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1.	Cao, Yang, Associate Professor, 1972-, et al. (författare) The statistical importance of P-POSSUM scores for predicting mortality after emergency laparotomy in geriatric patients 2020 Ingår i: BMC Medical Informatics and Decision Making. - : BioMed Central. - 1472-6947. ; 20:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Geriatric patients frequently undergo emergency general surgery and accrue a greater risk of postoperative complications and fatal outcomes than the general population. It is highly relevant to develop the most appropriate care measures and to guide patient-centered decision-making around end-of-life care. Portsmouth - Physiological and Operative Severity Score for the enumeration of Mortality and morbidity (P-POSSUM) has been used to predict mortality in patients undergoing different types of surgery. In the present study, we aimed to evaluate the relative importance of the P-POSSUM score for predicting 90-day mortality in the elderly subjected to emergency laparotomy from statistical aspects.METHODS: One hundred and fifty-seven geriatric patients aged ≥65 years undergoing emergency laparotomy between January 1st, 2015 and December 31st, 2016 were included in the study. Mortality and 27 other patient characteristics were retrieved from the computerized records of Örebro University Hospital in Örebro, Sweden. Two supervised classification machine methods (logistic regression and random forest) were used to predict the 90-day mortality risk. Three scalers (Standard scaler, Robust scaler and Min-Max scaler) were used for variable engineering. The performance of the models was evaluated using accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AUC). Importance of the predictors were evaluated using permutation variable importance and Gini importance.RESULTS: The mean age of the included patients was 75.4 years (standard deviation =7.3 years) and the 90-day mortality rate was 29.3%. The most common indication for surgery was bowel obstruction occurring in 92 (58.6%) patients. Types of post-operative complications ranged between 7.0-36.9% with infection being the most common type. Both the logistic regression and random forest models showed satisfactory performance for predicting 90-day mortality risk in geriatric patients after emergency laparotomy, with AUCs of 0.88 and 0.93, respectively. Both models had an accuracy > 0.8 and a specificity ≥0.9. P-POSSUM had the greatest relative importance for predicting 90-day mortality in the logistic regression model and was the fifth important predictor in the random forest model. No notable change was found in sensitivity analysis using different variable engineering methods with P-POSSUM being among the five most accurate variables for mortality prediction.CONCLUSION: P-POSSUM is important for predicting 90-day mortality after emergency laparotomy in geriatric patients. The logistic regression model and random forest model may have an accuracy of > 0.8 and an AUC around 0.9 for predicting 90-day mortality. Further validation of the variables' importance and the models' robustness is needed by use of larger dataset.
2.	Korjagina, M, et al. (författare) Prevalence of Serious Adverse Pregnancy Outcomes After Exposure to Interferon Beta Before or During Pregnancy: Stratification by Characteristics of Pregnant Women with MS in a Register-based Cohort study in Finland and Sweden 2020 Ingår i: NEUROLOGY. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 94:15 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
3.	Al Dabbagh, Z., et al. (författare) Long-term pattern of opioid prescriptions after femoral shaft fractures 2016 Ingår i: Acta Anaesthesiologica Scandinavica. - Hoboken, USA : Wiley-Blackwell. - 0001-5172 .- 1399-6576. ; 60:5, s. 634-641 Tidskriftsartikel (refereegranskat)abstract Background: The use of opioids in non-cancer-related pain following skeletal trauma is controversial due to the presumed risk of dose escalation and dependence. We therefore examined the pattern of opioid prescriptions, that is, those actually dispensed, in patients with femoral shaft fractures.Methods: We analysed data from the Swedish National Hospital Discharge Register and the Swedish Prescribed Drug Register between 2005 and 2008.Results: We identified 1471 patients with isolated femoral shaft fractures. The median age was 75 (16-102) years and 56% were female. In this cohort, 891 patients (61%) received dispensed opioid prescriptions during a median follow-up of 20 months (interquartile range 11-32). In the age- and sex-matched comparison cohort (7339 individuals) without fracture, 25% had opioid prescriptions dispensed during the same period. The proportions of patients receiving opioid analgesics at 6 and 12 months after the fracture were 45% (95% CI 42-49) and 36% (32-39), respectively. The median daily morphine equivalent dose (MED) was between 15 and 17 mg 1-12 months post-fracture. After 3 months, less than 5% used prescription doses higher than 20 mg MED per day. Older age (≥ 70 compared with < 70 years) was a significant predictor of earlier discontinuation of opioid use (Hazard ratio [HR] 1.9).Conclusion: A notable proportion of patients continued to receive dispensed prescriptions for opioids for over 6 months (45%) and more than a third of them (36%) continued treatment for at least 12 months. However, the risk of dose escalation seems to be small in opioid-naïve patients.
4.	Al Dabbagh, Zewar, et al. (författare) No signs of dose escalations of potent opioids prescribed after tibial shaft fractures : a study of Swedish National Registries 2014 Ingår i: BMC Anesthesiology. - London : BioMed Central. - 1471-2253 .- 1471-2253. ; 14, s. 4- Tidskriftsartikel (refereegranskat)abstract Background: The pattern of opioid use after skeletal trauma is a neglected topic in pain medicine. The purpose of this study was to analyse the long-term prescriptions of potent opioids among patients with tibial shaft fractures.Methods: Data were extracted from the Swedish National Hospital Discharge Register, the National Pharmacy Register, and the Total Population Register, and analysed accordingly. The study period was 2005-2008.Results: We identified 2,571 patients with isolated tibial shaft fractures. Of these, 639 (25%) collected a prescription for opioids after the fracture. The median follow-up time was 17 (interquartile range [IQR] 7-27) months. Most patients with opioid prescriptions after fracture were male (61%) and the median age was 45 (16-97) years. The leading mechanism of injury was fall on the same level (41%). At 6 and 12 months after fracture, 21% (95% CI 17-24) and 14% (11-17) were still being treated with opioids. Multiple Cox regression-analysis (adjusted for age, sex, type of treatment, and mechanism of injury) revealed that older patients (age >50 years) were more likely to end opioid prescriptions (Hazard ratio 1.5 [95% CI 1.3-1.9]). During follow-up, the frequency of patients on moderate and high doses declined. Comparison of the daily morphine equivalent dose among individuals who both had prescriptions during the first 3 months and the 6th month indicated that the majority of these patients (11/14) did not have dose escalations.Conclusions: We did not see any signs in registry-data of major dose escalations over time in patients on potent opioids after tibial shaft fractures.
5.	Arribas, Cristina, et al. (författare) Global cross-sectional survey on neonatal pharmacologic sedation and analgesia practices and pain assessment tools: impact of the sociodemographic index (SDI) 2024 Ingår i: Pediatric Research. - : Springer Nature. - 0031-3998 .- 1530-0447. Tidskriftsartikel (refereegranskat)
6.	Athlin, Åsa, 1971-, et al. (författare) Diagnostic spirometry in COPD is increasing, a comparison of two Swedish cohorts 2023 Ingår i: npj Primary Care Respiratory Medicine. - : Nature Publishing Group. - 2055-1010. ; 33:1 Tidskriftsartikel (refereegranskat)abstract Spirometry should be used to confirm a diagnosis of chronic obstructive pulmonary disease (COPD). This test is not always performed, leading to possible misdiagnosis. We investigated whether the proportion of patients with diagnostic spirometry has increased over time as well as factors associated with omitted or incorrectly interpreted spirometry. Data from medical reviews and a questionnaire from primary and secondary care patients with a doctors' diagnosis of COPD between 2004 and 2010 were collected. Data were compared with a COPD cohort diagnosed between 2000 and 2003. Among 703 patients with a first diagnosis of COPD between 2004 and 2010, 88% had a diagnostic spirometry, compared with 59% (p < 0.001) in the previous cohort. Factors associated with not having diagnostic spirometry were current smoking (OR 2.21; 95% CI 1.36-3.60), low educational level (OR 1.81; 1.09-3.02) and management in primary care (OR 2.28; 1.02-5.14). The correct interpretation of spirometry results increased (75% vs 82%; p = 0.010). Among patients with a repeated spirometry, 94% had a persistent FEV1/FVC or FEV1/VC ratio <0.70.
7.	Athlin, Åsa, 1971-, et al. (författare) Prediction of Mortality Using Different COPD Risk Assessments : A 12-Year Follow-Up 2021 Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - : Dove Medical Press Ltd.. - 1176-9106 .- 1178-2005. ; 16, s. 665-675 Tidskriftsartikel (refereegranskat)abstract Purpose: A multidimensional approach in the risk assessment of chronic obstructive pulmonary disease (COPD) is preferable. The aim of this study is to compare the prognostic ability for mortality by different COPD assessment systems; spirometric staging, classification by GOLD 2011, GOLD 2017, the age, dyspnea, obstruction (ADO) and the dyspnea, obstruction, smoking, exacerbation (DOSE) indices.Patients and Methods: A total of 490 patients diagnosed with COPD were recruited from primary and secondary care in central Sweden in 2005. The cohort was followed until 2017. Data for categorization using the different assessment systems were obtained through questionnaire data from 2005 and medical record reviews between 2000 and 2003. Kaplan-Meier survival analyses and Cox proportional hazard models were used to assess mortality risk. Receiver operating characteristic curves estimated areas under the curve (AUC) to evaluate each assessment systems´ ability to predict mortality.Results: By the end of follow-up, 49% of the patients were deceased. The mortality rate was higher for patients categorized as stage 3-4, GOLD D in both GOLD classifications and those with a DOSE score above 4 and ADO score above 8. The ADO index was most accurate for predicting mortality, AUC 0.79 (95% CI 0.75-0.83) for all-cause mortality and 0.80 (95% CI 0.75-0.85) for respiratory mortality. The AUC values for stages 1-4, GOLD 2011, GOLD 2017 and DOSE index were 0.73, 0.66, 0.63 and 0.69, respectively, for all-cause mortality.Conclusion: All of the risk assessment systems predict mortality. The ADO index was in this study the best predictor and could be a helpful tool in COPD risk assessment.
8.	Batyrbekova, Nurgul, et al. (författare) Hepatitis C virus infection and the temporal trends in the risk of liver cancer : a national register-based cohort study in Sweden 2020 Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:1, s. 63-70 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: In many countries, including Sweden, the birth cohorts with the highest prevalence of hepatitis C virus (HCV) infection have now reached the ages with high risk of primary liver cancer (PLC). The aims were to investigate the temporal trends in PLC incidence and the relative risks of PLC among people diagnosed with HCV-infection between 1990 and 2015.METHODS: The HCV-cohort (n: 52,853) was compared with a matched non-HCV comparison-cohort (n: 523,649). Both the Cancer (CR) and Death registers (DR) were used for follow-up. The crude and age-standardised PLC incidence rates were calculated. The relative risk was estimated as standardized incidence ratios (SIR) and as hazard ratios (HR) using stratified Cox hazards regression.RESULTS: There were 1,609 with PLC-diagnosis in the HCV-cohort, the annual number increased continuously with the crude incidence rate reaching 4.56 per 1,000 person-years in 2013, while remaining low and stable in the comparison-cohort. In the HCV-cohort, the age-standardised PLC incidence rates per 1,000 person-years remained relatively constant at 2.64 (95% CI: 1.54, 3.75) in 2000 and 3.31 (2.51, 4.12) in 2014. The highest SIR was 73 (65.9, 79.5) among those infected for 35-40 years; and the highest HR was 65.9 (55.9, 77.6) for men and 62.2 (31.9, 121.1) for women.CONCLUSIONS: There was a considerable increase in PLC-incidence over time and an extremely high relative risk in the population with HCV-infection for more than 35 years.IMPACT: The national HCV-associated PLC-incidence should be monitored in future studies to evaluate the effect of DAA-treatment.
9.	Bécares, Laia, et al. (författare) Bi-directional relationships between body mass index and height from three to seven years of age : an analysis of children in the United Kingdom Millennium Cohort Study 2016 Ingår i: Longitudinal and Life Course Studies. - London, England : Society for Longitudinal and Life Course Studies. - 1757-9597. ; 7:1, s. 41-52 Tidskriftsartikel (refereegranskat)abstract Adiposity and height are known to correlate in childhood but it is less clear whether height and weight gain occur in synergy. We investigate the bidirectional relationships between measures of height and body mass index (BMI) - an indicator of adiposity - and their rates of change. The sample comprises singleton children in the Millennium Cohort Study (N = 11,357). Child anthropometrics measured by trained interviewers at ages three, five and seven years (2003-2009) were transformed to standardised scores based on 1990 British Growth Reference data from which piecewise linear models for height and BMI were jointly fitted. At three years of age, zHeight was positively related to subsequent zBMI velocities, whereas zBMI at three years was positively related to zHeight velocity to age five but inversely related to zHeight velocity from five to seven years of age. Age three zBMI predicted zHeight velocity from three to five years more strongly than age three zHeight predicted zBMI velocity over the same period. The rate of change in zHeight was positively correlated with subsequent zBMI velocity and vice versa. This new evidence on the bidirectional relationships between height and BMI velocities sheds light on the early childhood origins of obesity in adulthood and the need to monitor growth as well as weight gain.
10.	Bejerot, Susanne, 1955-, et al. (författare) Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits) 2023 Ingår i: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 23:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years. Autoimmune diseases and severe infections are risk factors for the later development of schizophrenia, elevated inflammatory markers in childhood or adolescence are associated with a greater risk of schizophrenia in adulthood, individuals with schizophrenia have increased levels of pro-inflammatory cytokines compared to healthy controls, and autoimmune diseases are overrepresented in schizophrenia. However, treatments with anti-inflammatory agents are so far of doubtful clinical relevance. The primary objective of this study is to test whether the monoclonal antibody rituximab, directed against the B-cell antigen CD20 ameliorates psychotic symptoms in adults with schizophrenia or schizoaffective disorder and to examine potential mechanisms. A secondary objective is to examine characteristics of inflammation-associated psychosis and to identify pre-treatment biochemical characteristics of rituximab responders. A third objective is to interview a subset of patients and informants on their experiences of the trial to obtain insights that rating scales may not capture.METHODS: A proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of B-cell depletion in patients with psychosis. 120 participants with a diagnosis of schizophrenia spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion of rituximab (1000 mg) or saline. Psychiatric measures and blood samples will be collected at baseline, week 12, and week 24 post-infusion. Brief assessments will also be made in weeks 2 and 7. Neuroimaging and lumbar puncture, both optional, will be performed at baseline and endpoints. Approximately 40 of the patients and their informants will be interviewed for qualitative analyses on the perceived changes in well-being and emotional qualities, in addition to their views on the research.DISCUSSION: This is the first RCT investigating add-on treatment with rituximab in unselected SSD patients. If the treatment is helpful, it may transform the treatment of patients with psychotic disorders. It may also heighten the awareness of immune-psychiatric disorders and reduce stigma.TRIAL REGISTRATION: NCT05622201, EudraCT-nr 2022-000220-37 version 2.1. registered 14th of October 2022.
11.	Bergh, Cecilia, 1972-, et al. (författare) Determinants in adolescence of stroke-related hospital stay duration in men : a national cohort study 2016 Ingår i: Stroke. - Philadelphia, USA : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 47:9, s. 2416-2418 Tidskriftsartikel (refereegranskat)abstract Background and purpose: Physical and psychological characteristics in adolescence are associated with subsequent stroke risk. Our aim is to investigate their relevance to length of hospital stay and risk of second stroke.Methods: Swedish men born between 1952 and 1956 (n=237 879) were followed from 1987 to 2010 using information from population-based national registers. Stress resilience, body mass index, cognitive function, physical fitness, and blood pressure were measured at compulsory military conscription examinations in late adolescence. Joint Cox proportional hazards models estimated the associations of these characteristics with long compared with short duration of stroke-related hospital stay and with second stroke compared with first.Results: Some 3000 men were diagnosed with nonfatal stroke between ages 31 and 58 years. Low stress resilience, underweight, and higher systolic blood pressure (per 1-mm Hg increase) during adolescence were associated with longer hospital stay (compared with shorter) in ischemic stroke, with adjusted relative hazard ratios (and 95% confidence intervals) of 1.46 (1.08-1.89), 1.41 (1.04-1.91), and 1.01 (1.00-1.02), respectively. Elevated systolic and diastolic blood pressures during adolescence were associated with longer hospital stay in men with intracerebral hemorrhage: 1.01 (1.00-1.03) and 1.02 (1.00-1.04), respectively. Among both stroke types, obesity in adolescence conferred an increased risk of second stroke: 2.06 (1.21-3.45).Conclusions: Some characteristics relevant to length of stroke-related hospital stay and risk of second stroke are already present in adolescence. Early lifestyle influences are of importance not only to stroke risk by middle age but also to recurrence and use of healthcare resources among stroke survivors.
12.	Bergh, Cecilia, 1972-, et al. (författare) Non-psychotic mental disorders in adolescent men and risk of myocardial infarction : A national cohort study 2020 Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 41:Suppl. 2, s. 2812-2812 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Background/Purpose: Recent studies show that early life stress is associated with later risk of cardiovascular disease (CVD) and stress may also increase the risk of psychiatric disease. We investigated the association between non-psychotic mental disorders in adolescence and subsequent myocardial infarction, and the role of stress resilience and physical fitness in this association.Method: This is a register-based cohort study with 238 013 males born between 1952 and 1956 followed from 1987 to 2010 using information from Swedish registers. Stress resilience was measured at a compulsory military conscription examination using a semi-structured interview with a psychologist. Physical fitness was measured at conscription examination with a cycle ergometer test. A total of 34 503 men were diagnosed with a non-psychotic mental disorder at conscription. Using Cox regression, we estimated the association of mental disorders with myocardial infarction after adjustment for other established CVD risk factors in adolescence. Stress resilience and physical fitness were included in the adjusted model in a second set of analyses.Results: A total of 5891 diagnoses of first myocardial infarction were identified. Non-psychotic mental disorders were associated with an increased risk of myocardial infarction, with a hazard ratio (HR) and confidence interval (CI) of 1.51 (1.41–1.62). The association remained statistically significant after adjustment for other important potential confounders in adolescence such as systolic and diastolic blood pressure, body mass index, inflammation, cognitive function, parental socioeconomic index and a summary disease score (HR 1.24 (CI 1.13–1.35)). The association was further explained by stress resilience and lifestyle factors assessed with a cardiovascular fitness test in adolescence, as the association attenuated but remained statistically significant when further adjusting for stress resilience and physical fitness (HR 1.18 (CI 1.08–1.29)).Conclusion: A non-psychotic mental disorder in adolescences may increase the risk of developing myocardial infarction later in life. This association was partly but not completely explained by poorer stress resilience and physical fitness. Effective prevention might focus on behaviour/lifestyle and psychosocial stress in early life.
13.	Bergh, Cecilia, 1972-, et al. (författare) Pre-stroke characteristics and stroke severity after first stroke in middle-aged men 2015 Ingår i: Nordic Stroke 2015. Konferensbidrag (refereegranskat)
14.	Bergh, Cecilia, 1972-, et al. (författare) Severe infections and subsequent delayed cardiovascular disease 2017 Ingår i: European Journal of Preventive Cardiology. - : Sage Publications. - 2047-4873 .- 2047-4881. ; 24:18, s. 1958-1966 Tidskriftsartikel (refereegranskat)abstract Background: Severe infections in adulthood are associated with subsequent short-term cardiovascular disease. Whether hospital admission for sepsis or pneumonia is associated with persistent increased risk (over a year after infection) is less well established.Design: The design of this study was as a register-based cohort study.Methods: Some 236,739 men born between 1952-1956 were followed from conscription assessments in adolescence to 2010. All-cause cardiovascular disease ( n = 46,754), including coronary heart disease ( n = 10,279) and stroke ( n = 3438), was identified through national registers 1970-2010 (at ages 18-58 years).Results: Sepsis or pneumonia in adulthood (resulting in hospital admission) are associated with increased risk of cardiovascular disease in the years following infection. The risk is highest during the first year after the infection, with an adjusted hazard ratio (and 95% confidence intervals) of 6.33 (5.65-7.09) and a notably increased risk persisted with hazard ratios of 2.47 (2.04-3.00) for the second and 2.12 (1.71-2.62) for the third year after infection. The risk attenuated with time, but remained raised for at least five years after infection; 1.87 (1.47-2.38). The results are adjusted for characteristics in childhood, cardiovascular risk factors and medical history in adolescence. Similar statistically significant associations were found for coronary heart disease and stroke.Conclusions: Raised risks of cardiovascular disease following hospital admission for sepsis or pneumonia were increased for more than five years after the infection, but with the highest magnitude during the first three years following infection, suggesting a period of vulnerability when health professionals and patients should be aware of the heightened risk for cardiovascular disease.
15.	Bergh, Cecilia, 1972-, et al. (författare) Severe infections and subsequent delayed cardiovascular disease : national cohort study Annan publikation (övrigt vetenskapligt/konstnärligt)
16.	Bergh, Cecilia, 1972-, et al. (författare) Shared unmeasured characteristics among siblings confound the association of Apgar score with stress resilience in adolescence 2019 Ingår i: Acta Paediatrica. - : Wiley-Blackwell Publishing Inc.. - 0803-5253 .- 1651-2227. ; 108:11, s. 2001-2007 Tidskriftsartikel (refereegranskat)abstract AIM: We investigated the association between low Apgar score, other perinatal characteristics and low stress resilience in adolescence. A within-siblings analysis was used to tackle unmeasured shared familial confounding.METHODS: We used a national cohort of 527,763 males born in Sweden between 1973 and 1992 who undertook military conscription assessments at mean age 18 years (17-20). Conscription examinations included a measure of stress resilience. Information on Apgar score and other perinatal characteristics was obtained through linkage with the Medical Birth Register. Analyses were conducted using ordinary least squares and fixed-effects linear regression models adjusted for potential confounding factors.RESULTS: Infants with a prolonged low Apgar score at five minutes had an increased risk of low stress resilience in adolescence compared to those with highest scores at one minute, with an adjusted coefficient and 95% confidence interval of -0.26 (-0.39, -0.13). The associations were no longer statistically significant when using within-siblings models. However, the associations with stress resilience and birthweight remained statistically significant in all analyses.CONCLUSION: The association with low Apgar score seems to be explained by confounding due to shared childhood circumstances among siblings from the same family, while low birthweight is independently associated with low stress resilience.
17.	Bergh, Cecilia, 1972-, et al. (författare) Stress resilience and physical fitness in adolescence and risk of coronary heart disease in middle age 2015 Ingår i: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 101:8, s. 623-629 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Psychosocial stress is a suggested risk for coronary heart disease (CHD). The relationship of stress resilience in adolescence with subsequent CHD risk is underinvestigated, so our objective was to assess this and investigate the possible mediating role of physical fitness.METHODS: In this register-based study, 237 980 men born between 1952 and 1956 were followed from 1987 to 2010 using information from Swedish registers. Stress resilience was measured at a compulsory military conscription examination using a semistructured interview with a psychologist. Some 10 581 diagnoses of CHD were identified. Cox regression estimated the association of stress resilience with CHD, with adjustment for established cardiovascular risk factors.RESULTS: Low-stress resilience was associated with increased CHD risk. The association remained after adjustment for physical fitness and other potential confounding and mediating factors, with adjusted HRs (and 95% CIs) of 1.17 (1.10 to 1.25), with some evidence of mediation by physical fitness. CHD incidence rates per 1000 person-years (and 95% CIs) for low-stress, medium-stress and high-stress resilience were 2.61 (2.52 to 2.70), 1.97 (1.92 to 2.03) and 1.59 (1.53 to 1.67) respectively. Higher physical fitness was inversely associated with CHD risk; however, this was attenuated by low-stress resilience, shown by interaction testing (p<0.001).CONCLUSIONS: Low-stress resilience in adolescence was associated with increased risk of CHD in middle age and may diminish the benefit of physical fitness. This represents new evidence of the role of stress resilience in determining risk of CHD and its interrelationship with physical fitness.
18.	Bergh, Cecilia, 1972-, et al. (författare) Stress resilience in male adolescents and subsequent stroke risk : cohort study 2014 Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 85:12, s. 1331-1336 Tidskriftsartikel (refereegranskat)abstract Objective Exposure to psychosocial stress has been identified as a possible stroke risk, but the role of stress resilience which may be relevant to chronic exposure is uncertain. We investigated the association of stress resilience in adolescence with subsequent stroke risk.Methods Register-based cohort study. Some 237 879 males born between 1952 and 1956 were followed from 1987 to 2010 using information from Swedish registers. Cox regression estimated the association of stress resilience with stroke, after adjustment for established stroke risk factors.Results Some 3411 diagnoses of first stroke were identified. Lowest stress resilience (21.8%) compared with the highest (23.7%) was associated with increased stroke risk, producing unadjusted HR (with 95% CIs) of 1.54 (1.40 to 1.70). The association attenuated slightly to 1.48 (1.34 to 1.63) after adjustment for markers of socioeconomic circumstances in childhood; and after further adjustment for markers of development and disease in adolescence (blood pressure, cognitive function and pre-existing cardiovascular disease) to 1.30 (1.18 to 1.45). The greatest reduction followed further adjustment for markers of physical fitness (BMI and physical working capacity) in adolescence to 1.16 (1.04 to 1.29). The results were consistent when stroke was subdivided into fatal, ischaemic and haemorrhagic, with higher magnitude associations for fatal rather than non-fatal, and for haemorrhagic rather than ischaemic stroke.Conclusions Stress susceptibility and, therefore, psychosocial stress may be implicated in the aetiology of stroke. This association may be explained, in part, by poorer physical fitness. Effective prevention might focus on behaviour/lifestyle and psychosocial stress.
19.	Bergsten, Elisabet, et al. (författare) Confirmed efficacy of etoposide and dexamethasone in HLH treatment : long-term results of the cooperative HLH-2004 study 2017 Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 130:25, s. 2728-2738 Tidskriftsartikel (refereegranskat)abstract Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. In the HLH-94 study, with an estimated 5-year probability of survival (pSu) of 54% (95% confidence interval, 48%-60%), systemic therapy included etoposide, dexamethasone, and, from week 9, cyclosporine A (CSA). Hematopoietic stem cell transplantation (HSCT) was indicated in patients with familial/genetic, relapsing, or severe/persistent disease. In HLH-2004, CSA was instead administered upfront, aiming to reduce pre-HSCT mortality and morbidity. From 2004 to 2011, 369 children aged <18 years fulfilled HLH-2004 inclusion criteria (5 of 8 diagnostic criteria, affected siblings, and/or molecular diagnosis in FHL-causative genes). At median follow-up of 5.2 years, 230 of 369 patients (62%) were alive (5-year pSu, 61%; 56%-67%). Five-year pSu in children with (n = 168) and without (n = 201) family history/genetically verified FHL was 59% (52%-67%) and 64% (57%-71%), respectively (familial occurrence [n = 47], 58% [45%-75%]). Comparing with historical data (HLH-94), using HLH-94 inclusion criteria, pre-HSCT mortality was nonsignificantly reduced from 27% to 19% (P = .064 adjusted for age and sex). Time from start of therapy to HSCT was shorter compared with HLH-94 (P =020 adjusted for age and sex) and reported neurological alterations at HSCT were 22% in HLH-94 and 17% in HLH-2004 (using HLH-94 inclusion criteria). Five-year pSu post-HSCT overall was 66% (verified FHL, 70% [63%-78%]). Additional analyses provided specific suggestions on potential pre-HSCT treatment improvements. HLH-2004 confirms that a majority of patients may be rescued by the etoposide/dexamethasone combination but intensification with CSA upfront, adding corticosteroids to intrathecal therapy, and reduced time to HSCT did not improve outcome significantly.
20.	Björk, Tabita, 1966-, et al. (författare) Laterality, hand control and scholastic performance : a British birth cohort study 2012 Ingår i: BMJ Open. - London, United Kingdom : BMJ. - 2044-6055. ; 2:2, s. e000314- Tidskriftsartikel (refereegranskat)abstract Objectives: To use simple measures of laterality and hand control that can identify a greater risk of poorer scholastic ability, potentially signalling suboptimal hemispheric lateralisation.Design: Analysis of material from a birth cohort study.Setting: Members of the National Child Development Study, a British birth cohort study following people born in 1958.Participants: 10 612 children who undertook tests at age 11 years.Primary outcome measures: Teacher-administered tests of non-verbal general ability, verbal general ability, reading comprehension and mathematics. Results Linear regression produced associations (and 95% CIs) with tests of verbal general ability, non-verbal general ability, reading comprehension and mathematics scores for the lowest third (compared with highest) of a left-hand control test involving picking up matches of −1.21 (−1.73 to −0.68; p<0.001), −0.72 (−1.14 to −0.29; p=0.001), −0.70 (−1.06 to −0.35; p<0.001) and −1.32 (−1.90 to −0.73; p<0.001). Among those in the lowest third of the right-hand control test score, mixed-handedness compared with right-handedness was associated with poorer scholastic performance, with regression coefficients (and 95% CIs; p values) of 1.90 (−3.01 to −0.80; p=0.001), −1.25 (−2.15 to −0.35; p=0.007), −1.28 (2.04 to −0.53; p=0.001) and −1.33 (−2.53 to −0.13; p=0.030). The estimates are for a point change in the scholastic test scores, after adjustment for sex, left-hand motor function and social class. Statistically significant associations with mixed-handedness were only observed for the lowest third of right-hand motor function.Conclusions Measures involving poorer left-hand motor function may represent useful markers of reduced cognitive function possibly reflecting suboptimal hemispheric lateralisation. Crude measures of laterality such as reported non-right-handedness may be more useful for research when combined with measures of motor function.
21.	Bouhuis, Dennis, et al. (författare) Factors associated with self-assessed asthma severity 2022 Ingår i: Journal of Asthma. - : Marcel Dekker. - 0277-0903 .- 1532-4303. ; 59:4, s. 691-696 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Asthma severity can be estimated as the level of medication needed to achieve asthma control or by the patient's subjective assessment. Factors associated with self-assessed asthma severity are still incompletely explored.AIM: The aim was to study factors associated with self-assessed moderate or severe asthma.METHOD: In total, 1828 randomly selected asthma patients from primary (69%) and secondary (31%) care, completed a questionnaire including items about patient characteristics, comorbidity, the Asthma Control Test (ACT), emergency care visits and a scale for self-assessed asthma severity. Logistic regression was used to analyze associations with the dependent variable, self-assessed moderate or severe asthma in the entire study population and stratified by sex.RESULTS: Of the patients, 883 (45%) reported having moderate or severe asthma. Factors independently associated with self-assessed moderate or severe asthma were age >60 years (OR [95% CI] 1.98 [1.37-2.85]), allergic rhino-conjunctivitis (1.43 [1.05-1.95]), sinusitis (1.45 [1.09-1.93]), poor asthma control as measured by ACT <20 (5.64 [4.45-7.16]) and emergency care visits the previous year (2.52 [1.90-3.34]). Lower level of education was associated with self-assessed moderate/severe asthma in women (1.16 [1.05-2.43]) but not in men (0.90 [0.65-1.25]), p for interaction = .012.CONCLUSION: Poor asthma control, allergic rhino-conjunctivitis, recent sinusitis and older age were independently associated with self-assessed moderate or severe asthma. Important implications are that comorbid conditions of the upper airways should always be considered as part of asthma management, and that elderly patients may need extra attention.
22.	Bouhuis, Dennis, et al. (författare) Factors Associated with the Non-Exacerbator Phenotype of Chronic Obstructive Pulmonary Disease 2023 Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - : Dove Medical Press Ltd.. - 1176-9106 .- 1178-2005. ; 18, s. 483-492 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) and no exacerbations may need less maintenance treatment and follow-up. The aim was to identify factors associated with a non-exacerbator COPD phenotype.METHODS: Cross-sectional analysis of 1354 patients from primary and secondary care, with a doctor's diagnosis of COPD. In 2014, data on demographics, exacerbation frequency and symptoms using COPD Assessment Test (CAT) were collected using questionnaires and on spirometry and comorbid conditions by record review. The non-exacerbator phenotype was defined as having reported no exacerbations the previous six months. Multivariable logistic regression with the non-exacerbator phenotype as dependent variable was performed, including stratification and interaction analyses by sex.RESULTS: The non-exacerbator phenotype was found in 891 (66%) patients and was independently associated with COPD stage 1 (OR [95% CI] 5.72 [3.30-9.92]), stage 2 (3.42 [2.13-5.51]) and stage 3 (2.38 [1.46-3.88]) compared with stage 4, and with CAT score <10 (3.35 [2.34-4.80]). Chronic bronchitis and underweight were inversely associated with the non-exacerbator phenotype (0.47 [0.28-0.79]) and (0.68 [0.48-0.97]), respectively. The proportion of non-exacerbators was higher among patients with no maintenance treatment or a single bronchodilator. The association of COPD stage 1 compared with stage 4 with the non-exacerbator phenotype was stronger in men (p for interaction 0.048). In women, underweight and obesity were both inversely associated with the non-exacerbator phenotype (p for interaction 0.033 and 0.046 respectively), and in men heart failure was inversely associated with the non-exacerbator phenotype (p for interaction 0.030).CONCLUSION: The non-exacerbator phenotype is common, especially in patients with no maintenance treatment or a single bronchodilator, and is characterized by preserved lung function, low symptom burden, and by absence of chronic bronchitis, underweight and obesity and heart failure. We suggest these patients may need less treatment and follow-up, but that management of comorbid conditions is important to avoid exacerbations.
23.	Brand, Judith, 1984-, et al. (författare) Additional Counseling Support for Mothers With Gestational Hypertensive Disorders Regarding Neurodevelopmental Outcomes in Their Children—Reply 2021 Ingår i: JAMA pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 175:10 Tidskriftsartikel (refereegranskat)
24.	Brand, Judith, 1984-, et al. (författare) Association Between Hypertensive Disorders of Pregnancy and Neurodevelopmental Outcomes Among Offspring 2021 Ingår i: JAMA pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 175:6, s. 577-585 Tidskriftsartikel (refereegranskat)abstract Importance: Hypertensive disorders of pregnancy (HDP) have been associated with poorer neurodevelopmental outcomes in offspring, but the role of familial confounding in these associations is unclear.Objective: To investigate associations of maternal HDP with risks in offspring of autism spectrum disorders (ASDs), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID), as well as variation in overall cognitive performance in offspring.Design, Setting, and Participants: This Swedish register-based study used data from a birth cohort divided into 1 085 024 individuals born between 1987 and 1996 and followed up until December 31, 2014, and 285 901 men born between 1982 and 1992 who attended assessments for military conscription, including a cognitive function test. Statistical analysis was performed from April 1, 2019, to June 1, 2020.Exposures: Diagnoses of HDP, which were provided by the Medical Birth Register.Main Outcomes and Measures: Diagnoses of ASDs, ADHD, and ID were extracted from the National Patient Register. Cognitive function was assessed using written tests and summarized as a single 9-point score. Whole-cohort and within-sibship analyses were performed; the latter accounted for unmeasured familial confounding factors shared by siblings.Results: The study included 1 085 024 individuals (556 912 male participants [51.3%]) born between 1987 and 1996 and 285 901 men born between 1982 and 1992 who attended assessments for military conscription. The prevalence of maternal HDP was 4.0% in the 1987-1996 birth cohort (n = 42 980) and 5.1% in the military conscription cohort (n = 14 515). A total of 15 858 participants received a diagnosis of ASD, 36 852 received a diagnosis of ADHD, and 8454 received a diagnosis of ID. The mean (SD) cognitive score among the men in the conscription cohort was 5.1 (1.9). In whole-cohort analyses with multivariable adjustment, HDP were associated with offspring ASDs (hazard ratio [HR], 1.22; 95% CI, 1.13-1.31), ADHD (HR, 1.10; 95% CI, 1.05-1.16), and ID (HR, 1.39; 95% CI, 1.27-1.53). Analyses comparing siblings discordant for HDP were less statistically powered but indicated estimates of similar magnitude for ASDs (HR, 1.19; 95% CI, 1.00-1.42) and possibly ADHD (HR, 1.09; 95% CI, 0.95-1.24), but not for ID (HR, 1.04; 95% CI, 0.83-1.29). Hypertensive disorders of pregnancy were associated with somewhat lower cognitive scores in whole-cohort analysis (mean difference comparing offspring exposed with those unexposed, -0.10; 95% CI, -0.13 to -0.07), but in within-sibship analysis, the association was null (mean difference, 0.00; 95% CI, -0.09 to 0.08).Conclusions and Relevance: The study results suggest that HDP are associated with small increased risks of ASDs and possibly ADHD in offspring, whereas associations with ID and cognitive performance are likely confounded by shared familial (environmental or genetic) factors.
25.	Brand, Judith, 1984-, et al. (författare) Maternal smoking during pregnancy and fractures in offspring : national register based sibling comparison study 2020 Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 368 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To study the impact of maternal smoking during pregnancy on fractures in offspring during different developmental stages of life.DESIGN: National register based birth cohort study with a sibling comparison design.SETTING: Sweden.PARTICIPANTS: 1 680 307 people born in Sweden between 1983 and 2000 to women who smoked (n=377 367, 22.5%) and did not smoke (n=1 302 940) in early pregnancy. Follow-up was until 31 December 2014.MAIN OUTCOME MEASURE: Fractures by attained age up to 32 years.RESULTS: During a median follow-up of 21.1 years, 377 970 fractures were observed (the overall incidence rate for fracture standardised by calendar year of birth was 11.8 per 1000 person years). The association between maternal smoking during pregnancy and risk of fracture in offspring differed by attained age. Maternal smoking was associated with a higher rate of fractures in offspring before 1 year of age in the entire cohort (birth year standardised fracture rates in those exposed and unexposed to maternal smoking were 1.59 and 1.28 per 1000 person years, respectively). After adjustment for potential confounders the hazard ratio for maternal smoking compared with no smoking was 1.27 (95% confidence interval 1.12 to 1.45). This association followed a dose dependent pattern (compared with no smoking, hazard ratios for 1-9 cigarettes/day and >= 10 cigarettes/day were 1.20 (95% confidence interval 1.03 to 1.39) and 1.41 (1.18 to 1.69), respectively) and persisted in within-sibship comparisons although with wider confidence intervals (compared with no smoking, 1.58 (1.01 to 2.46)). Maternal smoking during pregnancy was also associated with an increased fracture incidence in offspring from age 5 to 32 years in whole cohort analyses, but these associations did not follow a dose dependent gradient. In within-sibship analyses, which controls for confounding by measured and unmeasured shared familial factors, corresponding point estimates were all close to null. Maternal smoking was not associated with risk of fracture in offspring between the ages of 1 and 5 years in any of the models.CONCLUSION: Prenatal exposure to maternal smoking is associated with an increased rate of fracture during the first year of life but does not seem to have a long lasting biological influence on fractures later in childhood and up to early adulthood.
26.	Brand, Judith S, et al. (författare) Risk of serious infections in multiple sclerosis patients by disease course and disability status : Results from a Swedish register-based study 2022 Ingår i: Brain, behavior, & immunity - health. - : Elsevier. - 2666-3546. ; 22 Tidskriftsartikel (refereegranskat)abstract Background and objectives: Serious infections are an emerging concern with increasing use of potent immunomodulation in multiple sclerosis (MS), but the extent to which MS disease features influence infectious susceptibility is poorly characterized. The objective of this study was to assess the associations of MS disease course and disability status with risk of serious infections.Methods: A cohort of 8660 MS patients was individually matched on age, sex and region of residence with 86,600 people without MS from the general population using national registers in Sweden. The study period was from 1996 to 2012, with follow-up until December 31, 2014. The main outcomes were infection as the underlying or contributory cause of death or infection-related hospital admission identified in the Cause of Death and Patient registers. MS disease course (relapsing-remitting or progressive disease) and Expanded Disability Status Scale (EDSS) score (six and over or below six) were extracted from the MS Register Hazard ratios (HRs) for any serious infection were estimated using flexible parametric models.Results: During a median follow-up of 9.6 years (interquartile range = 5.5-13.5 years), 1337 MS patients experienced a serious infection. Compared with individually matched people without MS, risk of serious infection was greater for progressive disease (HR = 3.80; 95% CI 3.52: 4.09) than relapsing-remitting disease (HR = 1.77; 95% CI: 1.62:1.93). A similar pattern of risk was seen for dichotomised EDSS score (HR = 4.26; 95% CI 3.87: 4.70 for EDSS 6.0-9.5 and HR = 1.30; 95% CI 1.1853: 1.43 for EDSS 0.0-5.5). Overall, associations with greater disability did not notably differ by immunomodulatory therapy use, but associations with lower disability were more pronounced in patients receiving these therapies.Conclusions: Disease course or EDSS score (which may be more readily available than MS course in some patients) should be considered in individual management and monitoring of MS patients, including assessing benefit-risk of therapies that influence general immune function.
27.	Brenner, P., et al. (författare) Multiple sclerosis and risk of attempted and completed suicide : a cohort study 2016 Ingår i: European Journal of Neurology. - Hoboken, USA : Wiley-Blackwell Publishing Inc.. - 1351-5101 .- 1468-1331. ; 23:8, s. 1329-1336 Tidskriftsartikel (refereegranskat)abstract Background and purpose: Patients with multiple sclerosis (MS) are known to have an elevated suicide risk, but attempted suicide is incompletely investigated. The relation between education level and suicidality has not been investigated in MS patients. Our objective was to estimate attempted suicide and completed suicide risks amongst MS patients.Methods: A total of 29 617 Swedish MS patients were identified through the Swedish Patient Register and matched with 296 164 people without MS from the general population. Cox regression analysis estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of MS with attempted and completed suicide, with adjustment for age, sex, education and calendar period.Results: The adjusted HR for attempted suicide amongst MS patients is 2.18 (95% CI 1.97-2.43) compared with the general population cohort. For completed suicide the HR is 1.87 (95% CI 1.53-2.30). In both groups women are at higher risk of attempting suicide, whilst men are at higher risk of completing suicide. Education level is inversely associated with completed suicide amongst the non-MS cohort (0.68, 0.51-0.91), but not amongst MS patients (1.10, 0.60-2.04).Conclusion: Multiple sclerosis patients are at higher risk of both attempted and completed suicide. No evidence was found of an inverse association between educational level and risk of completed suicide amongst MS patients.
28.	Brenner, P., et al. (författare) Multiple sclerosis and risk of completed and attempted suicide - a national cohort study 2015 Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 21:Suppl. 11, s. 23-24 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Introduction: Patients with multiple sclerosis (MS) are known to have an elevated suicide risk, but attempted suicide is incompletely investigated.Objectives: To estimate attempted suicide and completed suicide risks among MS patients using national registers and to assess if the inverse association of higher-level education with completed suicide is affected by MS.Methods: A total of 29,617 Swedish MS patients were identified through the Swedish Patient Register and matched (by birth year, sex, vital status at diagnosis and region) with 296,164 people without MS from the general population. Cox regression estimated hazard ratios (HR) (with 95% confidence intervals) for the association of MS with attempted and completed suicide, with adjustment for age, sex, education level, decade of study entry, and previous suicide attempts.Results: The adjusted HR for attempted suicide among MS patients is 2.18 (1.97-2.43) compared with the general population cohort. For completed suicide the HR is 1.87 (1.53-2.30). Overall, men were at higher risk of completing suicide, while women were at higher risk of attempting suicide. Higher education is inversely associated with completed suicide among the non-MS cohort with an HR of 0.68, (0.51-0.91), but not among MS patients, where the HR is 1.10, (0.60-2.04). MS patients were less likely to use a violent method than the non-MS cohort.Conclusion: MS patients are at higher risk of both attempted and completed suicide, and the risk increase is present in both men and women. Possibly the stress and perceived prognosis associated with an MS diagnosis increases the risk of suicide. MS appears to eliminate the protective association of higher education with completed suicide.
29.	Burkill, Sarah M., et al. (författare) Pain and Painkiller Use Among Multiple Sclerosis Patients in Sweden 2017 Ingår i: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 26:Suppl. 2, s. 634-634 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Background: Multiple sclerosis is an autoimmune disease which leads to demyelination and subsequent damage of axons and neurons. Pain is known to commonly affect MS patients, however the clinical characteristics of this pain are not fully described. Prescribed pain medication identifies more severe and chronic pain and different drug types can be used to identify other pain characteristics.Objectives: To assess whether MS patients in Sweden are at increased risk of receiving medication for pain relative to non-MS comparators. We aim to study overall pain, neuropathic pain, musculoskeletal pain and migraine.Methods: This cohort study using data on 5,555 MS patients in Sweden individually matched to 5,555 non-MS Swedish residents on sex, year of birth and place of residence at the time of MS diagnosis. We used Cox PH models using date of entry or 1stJuly 2006 as the beginning of follow up, whichever occurred later, and end of study was date of death, date of prescription of a painkiller or December 31st 2014, whichever occurred first. Painkillers were identified through relevant ATC codes. For neuropathic pain, pregabalin, gabapentin, amitriptyline, capsaicin or nortriptyline were used for identification, and for migraine prescriptions of anti-migraine preparations were included in the outcome. Musculoskeletal pain was identified primarily through topical products for joint and muscular pain.Results: Cox PH models showed MS patients to be at a 2.43 (CI 2.31–2.55) times increased risk of being prescribed any painkiller. The risk increased to 5.63 (CI 5.03–6.31) for neuropathic painkillers, however there was no significant difference for musculoskeletal painkillers (RR = 0.92 (CI 0.79–1.07)). MS patients were at a 1.28 (CI 1.10-1.50) times increased risk of being prescribed anti-migraine preparations. Restricting the data to MS patients showed that exposure to neuropathic painkillers was present in 32.8% of MS patients, and is associated with lower educational attainment and female sex. Conclusions: MS patients are at significantly increased risk of pain overall, with a particularly elevated risk for neuropathic pain. It seems that lower educational attainment and female sex are risk factors of neuropathic pain. However, the reason for this is not fully understood.*We would like to acknowledge the funding from the Science for Life - Astra Zeneca collaborative grant that supported this research
30.	Burkill, Sarah, et al. (författare) Mortality trends for multiple sclerosis patients in Sweden from 1968 to 2012 2017 Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 89:6, s. 555-562 Tidskriftsartikel (refereegranskat)abstract Objective: To assess trends in mortality and causes of death for patients with multiple sclerosis (MS) relative to those without MS in Sweden.Methods: Patients with an MS diagnosis in Sweden between 1964 and 2012 were identified with the Patient Register and the Multiple Sclerosis Register. For this cohort study, each patient with MS (n = 29,617) was matched with 10 individuals without MS (n = 296,164) on sex, year of birth, vital status, and region of residence at the time of MS diagnosis with the Total Population Register. The Causes of Death Register was used to identify causes of death. Cox proportional hazard models were constructed to assess whether risk of mortality was increased for patients with MS.Results: The hazard ratio (HR) for patients with MS was 2.92 (95% confidence interval [CI] 2.86-2.99) for all-cause mortality over the entire study period. The largest differences between the cohorts were death resulting from respiratory (HR 5.07, 95% CI 4.87-5.26) and infectious (HR 4.07, 95% CI 3.70-4.47) diseases. Overall and for each specific cause, there have been improvements for the MS group and a subsequent reduction in the HR. The HR decreased from 6.52 (95% CI 5.79-7.34) for the period of 1968 to 1980 to 2.08 (95% CI 1.95-2.22) for the time period of 2001 to 2012. An interaction between time period and MS exposure showed that the decrease in mortality over time was statistically significant, with a larger decrease for patients with MS than their matched comparators.Conclusions: There has been a substantial improvement in mortality overall and for each specified cause of death for patients with MS compared with individuals without MS; however, large differences still remain.
31.	Burkill, S., et al. (författare) MS and the association of the DQB10302 allele with pain 2019 Ingår i:* Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 437-438 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Introduction: There is an established association between multiple sclerosis (MS) and pain treatment, in particular neuropathic pain. Murine models have confirmed an association between carriage of the DQB10302 allele and development of neuropathic pain-like behavior after peripheral nerve injury. Observational studies in patients with spinal disc herniation identified an association between the DQB10302 allele and pain, indicating a possible link in humans. This HLA allele has not been previously investigated for its influence on susceptibility to pain in MS patients.Aim: To determine whether the DQB10302 genotype is associated with pain in MS patients or member of the general population without MS.Methods: Three Swedish studies (EIMS, GEMS and IMSE) were combined in which enrolled MS patients were matched with 1-2 randomly selected individuals without MS by sex, age and region of residence. Register data was obtained and prescriptions for pain and neuropathic pain were identified as proxy measures for pain. Blood samples were collected and genotyped. Individuals were included if genotype data were available (MS=3877, non-MS=4548). Logistic regression had pain medication use as the outcome, to examine associations with genotype, stratified by MS status.Results: Homo- or heterozygous MS patients with the DQB10302 allele had no significantly increased risk of pain (adjusted OR 1.02, 95% CI 0.85-1.23) or neuropathic pain (OR 1.14, 0.97-1.34) compared with MS patients without the allele. Non-MS comparators carrying at least one allele had an increased risk of pain (OR 1.18, 1.03-1.35). Additionally, a zygosity effect appeared present particularly for women in the non-MS cohort, as homozygous individuals had a higher risk of pain compared with heterozygotes. No association was observed for MS patients.Conclusions: The DQB1*0302 allele was associated with increased risk of pain among the non-MS cohort. Zygocity also impacted on pain risk in this cohort, particularly for women. The same was not observed in MS patients, for which no increased risk was detected. In view of previous data, immune functions seem to be involved in the development of pain and the observed associa-tion is likely due to peripheral nerve injuries or peripheral neu-ropathies. The allele was not associated with pain in the MS population, which often stems from CNS lesions.
32.	Burkill, Sarah, et al. (författare) Pharmacological Treatments Preceding Diagnosis Of Progressive Multifocal Leukencephalopathy 2016 Ingår i: Pharmacoepidemiology and Drug Safety. - : Wiley-Blackwell. - 1053-8569 .- 1099-1557. ; 25:Suppl. 3, s. 496-497 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Background: Progressive multifocal leukencephalopathy (PML) is a rare, often fatal viral disease, which affects the white matter of the brain. It is caused by John Cunningham (JC) polyomavirus, which is present in most people and is usually harm-less. For immunocompromised persons, such as those who are taking immunosuppressive treatments, the risk of JC virus causing PML is increased, although still rare. As PML diagnosis is not always accurate, epidemiology of PML, including the true incidence and patient characteristics, is incompletely described.Objectives: To identify pharmacological treatments preceding diagnosis of deﬁnitive, probable and possible PML, after excluding incorrect PML diagnoses by medical record review.Methods: Patients with a PML diagnosis in Sweden between 1988 and 2013 were identiﬁed through the Patient register using ICD 9 code 046D and ICD 10code A81.2 (n = 281). Medical records were reviewed and information on clinical characteristics and pharmacological treatments were collected. Each of the diagnoses was determined as deﬁnite PML, possible PML, probable PML or non-PML based on the consensus statement for the AAN neuroinfectious disease section published in 2013. (PMCID: 3662270).Results: Medical records for 251 patients (89%) were available and examined. In total, 84 (33%) of the 251 PML diagnoses were conﬁrmed. For those with a record of being exposed to immunosuppressant drugs, 60 (65%) of the 92 records were conﬁrmed as being deﬁnite PML. Among 12 patients exposed to rituximab 11 (92%) had deﬁnite and 1 (8%) had probable PML. For the 9 natalizumab users, 8 (89%) had deﬁnite PML and 1 (11%) was diagnosed incorrectly.Conclusions: A substantial proportion of PML diagnoses recorded in Sweden are incorrect, however amongst those exposed to immunosuppressants such as rituximab and natalizumab the majority of diagnoses are correct. Assessing immunosuppressive drug history could be an important part of the diagnostic processes for PML.
33.	Burkill, Sarah, et al. (författare) The association between exposure to interferon-beta during pregnancy and birth measurements in offspring of women with multiple sclerosis 2019 Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 28:Suppl. 2, s. 371-372 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Interferon-beta (IFN-beta) is a commonly used treatment for multiple sclerosis (MS). Current guidelines recommend cessation of treatment during pregnancy, however the results of past studies on the safety of prenatal exposure to IFN-beta have been conflicting. A large scale study of a population of MS women is therefore warranted.OBJECTIVES: To assess whether, among those born to women with MS, infants prenatally exposed to IFN-beta show evidence of smaller size at birth relative to infants which were not prenatally exposed to any MS disease modifying drugs.METHODS: Swedish and Finnish register data was used. Births to women with MS in Sweden and Finland between 2005-2014 for which a birth measurement for weight, height, and head circumference was available were included. The exposure window was from 6 months prior to LMP to the end of pregnancy.RESULTS: In Sweden, 411 pregnancies were identified as exposed to IFN-beta during the exposure window, and 835 pregnancies were counted as unexposed to any MS DMD. The corresponding numbers for Finland were 232 and 331 respectively. Infants prenatally exposed to interferon-beta were on average 28 grams heavier (p = 0.17), 0.01 cm longer (p = 0.95), and had head circumferences 0.14 cm larger (p = 0.13) in Sweden. In Finland, infants were 50 grams lighter (p = 0.27), 0.02 cm shorter (p = 0.92) and had head circumferences 0.22 cm smaller (p = 0.15) relative to those unexposed.CONCLUSIONS: This study provides evidence that exposure to IFN-beta during pregnancy does not influence birth weight, length, or head circumference.
34.	Burkill, Sarah, et al. (författare) The association between multiple sclerosis and pain medications 2019 Ingår i: Pain. - : Lippincott Williams & Wilkins. - 0304-3959 .- 1872-6623. ; 160:2, s. 424-432 Tidskriftsartikel (refereegranskat)abstract Patients with multiple sclerosis (MS) are at greater risk of pain than people without the disease; however, the occurrence and characteristics of pain among these patients are incompletely described. We aimed to assess characteristics of pain amongst MS patients using MS patients who were recruited to participate in 3 studies in Sweden (n = 3877) and were matched with individuals without MS (n = 4548) by sex, year of birth, and region of residence. The Prescribed Drugs Register identified prescribed pain medication, overall and restricted to those given 4 or more prescriptions in 1 year to assess chronic pain. Anatomical therapeutic chemical codes classified whether pain was neuropathic, musculoskeletal, or migraine. Cox-proportional hazard models were used to estimate associations. Our findings showed patients with MS were at increased risk of pain treatment, with a hazard ratio (HR) of 2.52 (95% confidence interval 2.38-2.66). The largest magnitude HR was for neuropathic pain (5.73, 5.07-6.47) for which 34.2% (n = 1326) of the MS and 7.15% (n = 325) of the non-MS cohort were prescribed a treatment. The HR for chronic pain treatment was 3.55 (3.27-3.84), indicating an increased effect size relative to any pain treatment. Chronic neuropathic pain showed the largest HR at 7.43 (6.21-8.89). Neuropathic pain was shown to be the primary mechanism leading to increased risk of pain in patients with MS.
35.	Burkill, Sarah, et al. (författare) The DQB1* 03:02 Genotype and Treatment for Pain in People With and Without Multiple Sclerosis 2020 Ingår i: Frontiers in Neurology. - : Frontiers. - 1664-2295. ; 11 Tidskriftsartikel (refereegranskat)abstract Murine models have demonstrated that the major histocompatibility complex (MHC) is associated with pain-like behavior in peripheral nerve injury, however, the same association has not been shown when considering injury to the central nervous system (CNS), which more closely mimics the damage to the CNS experienced by MS patients. Previous research has indicated the DQB103:02 allele of the class II HLA genes as being associated with development of neuropathic pain in persons undergoing inguinal hernia surgery or with lumbar spinal disk herniation. Whether this HLA allele plays a part in susceptibility to pain, has not, as far as we are aware, been previously investigated. This study utilizes information on DQB103:02 alleles as part of the EIMS, GEMS, and IMSE studies in Sweden. It also uses register data for 3,877 MS patients, and 4,548 matched comparators without MS, to assess whether the DQB103:02 allele is associated with prescribed pain medication use, and whether associations with this genotype differ depending on MS status. Our results showed no association between the DQB103:02 genotype and pain medication in MS patients, with an adjusted odds ratio (OR) of 1.02 (95% CI 0.85-1.24). In contrast, there was a statistically significant association of low magnitude in individuals without MS [adjusted OR 1.18 (95% CI 1.03-1.35)], which provides support for HLA influence on susceptibility to pain in the general population. Additionally, the effect of zygosity was evident for the non-MS cohort, but not among MS patients, suggesting the DQB1*03:02 allele effect is modified by the presence of MS.
36.	Cao, Yang, Associate Professor, 1972-, et al. (författare) COVID-19 case-fatality rate and demographic and socioeconomic influencers : worldwide spatial regression analysis based on country-level data 2020 Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 10:11 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To investigate the influence of demographic and socioeconomic factors on the COVID-19 case-fatality rate (CFR) globally.DESIGN: Publicly available register-based ecological study.SETTING: Two hundred and nine countries/territories in the world.PARTICIPANTS: Aggregated data including 10 445 656 confirmed COVID-19 cases.PRIMARY AND SECONDARY OUTCOME MEASURES: COVID-19 CFR and crude cause-specific death rate were calculated using country-level data from the Our World in Data website.RESULTS: The average of country/territory-specific COVID-19 CFR is about 2%-3% worldwide and higher than previously reported at 0.7%-1.3%. A doubling in size of a population is associated with a 0.48% (95% CI 0.25% to 0.70%) increase in COVID-19 CFR, and a doubling in the proportion of female smokers is associated with a 0.55% (95% CI 0.09% to 1.02%) increase in COVID-19 CFR. The open testing policies are associated with a 2.23% (95% CI 0.21% to 4.25%) decrease in CFR. The strictness of anti-COVID-19 measures was not statistically significantly associated with CFR overall, but the higher Stringency Index was associated with higher CFR in higher-income countries with active testing policies (regression coefficient beta=0.14, 95% CI 0.01 to 0.27). Inverse associations were found between cardiovascular disease death rate and diabetes prevalence and CFR.CONCLUSION: The association between population size and COVID-19 CFR may imply the healthcare strain and lower treatment efficiency in countries with large populations. The observed association between smoking in women and COVID-19 CFR might be due to the finding that the proportion of female smokers reflected broadly the income level of a country. When testing is warranted and healthcare resources are sufficient, strict quarantine and/or lockdown measures might result in excess deaths in underprivileged populations. Spatial dependence and temporal trends in the data should be taken into account in global joint strategy and/or policy making against the COVID-19 pandemic.
37.	Cao, Yang, Associate Professor, 1972-, et al. (författare) Deep Learning Neural Networks to Predict Serious Complications After Bariatric Surgery : Analysis of Scandinavian Obesity Surgery Registry Data 2020 Ingår i: JMIR Medical Informatics. - : JMIR Publications. - 2291-9694. ; 8:5 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Obesity is one of today's most visible public health problems worldwide. Although modern bariatric surgery is ostensibly considered safe, serious complications and mortality still occur in some patients.OBJECTIVE: This study aimed to explore whether serious postoperative complications of bariatric surgery recorded in a national quality registry can be predicted preoperatively using deep learning methods.METHODS: Patients who were registered in the Scandinavian Obesity Surgery Registry (SOReg) between 2010 and 2015 were included in this study. The patients who underwent a bariatric procedure between 2010 and 2014 were used as training data, and those who underwent a bariatric procedure in 2015 were used as test data. Postoperative complications were graded according to the Clavien-Dindo classification, and complications requiring intervention under general anesthesia or resulting in organ failure or death were considered serious. Three supervised deep learning neural networks were applied and compared in our study: multilayer perceptron (MLP), convolutional neural network (CNN), and recurrent neural network (RNN). The synthetic minority oversampling technique (SMOTE) was used to artificially augment the patients with serious complications. The performances of the neural networks were evaluated using accuracy, sensitivity, specificity, Matthews correlation coefficient, and area under the receiver operating characteristic curve.RESULTS: In total, 37,811 and 6250 patients were used as the training data and test data, with incidence rates of serious complication of 3.2% (1220/37,811) and 3.0% (188/6250), respectively. When trained using the SMOTE data, the MLP appeared to have a desirable performance, with an area under curve (AUC) of 0.84 (95% CI 0.83-0.85). However, its performance was low for the test data, with an AUC of 0.54 (95% CI 0.53-0.55). The performance of CNN was similar to that of MLP. It generated AUCs of 0.79 (95% CI 0.78-0.80) and 0.57 (95% CI 0.59-0.61) for the SMOTE data and test data, respectively. Compared with the MLP and CNN, the RNN showed worse performance, with AUCs of 0.65 (95% CI 0.64-0.66) and 0.55 (95% CI 0.53-0.57) for the SMOTE data and test data, respectively.CONCLUSIONS: MLP and CNN showed improved, but limited, ability for predicting the postoperative serious complications after bariatric surgery in the Scandinavian Obesity Surgery Registry data. However, the overfitting issue is still apparent and needs to be overcome by incorporating intra- and perioperative information.
38.	Cao, Yang, Associate Professor, 1972-, et al. (författare) Development and Validation of an XGBoost-Algorithm-Powered Survival Model for Predicting In-Hospital Mortality Based on 545,388 Isolated Severe Traumatic Brain Injury Patients from the TQIP Database 2023 Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 13:9 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Traumatic brain injury (TBI) represents a significant global health issue; the traditional tools such as the Glasgow Coma Scale (GCS) and Abbreviated Injury Scale (AIS) which have been used for injury severity grading, struggle to capture outcomes after TBI.AIM AND METHODS: This paper aims to implement extreme gradient boosting (XGBoost), a powerful machine learning algorithm that combines the predictions of multiple weak models to create a strong predictive model with high accuracy and efficiency, in order to develop and validate a predictive model for in-hospital mortality in patients with isolated severe traumatic brain injury and to identify the most influential predictors. In total, 545,388 patients from the 2013-2021 American College of Surgeons Trauma Quality Improvement Program (TQIP) database were included in the current study, with 80% of the patients used for model training and 20% of the patients for the final model test. The primary outcome of the study was in-hospital mortality. Predictors were patients' demographics, admission status, as well as comorbidities, and clinical characteristics. Penalized Cox regression models were used to investigate the associations between the survival outcomes and the predictors and select the best predictors. An extreme gradient boosting (XGBoost)-powered Cox regression model was then used to predict the survival outcome. The performance of the models was evaluated using the Harrell's concordance index (C-index). The time-dependent area under the receiver operating characteristic curve (AUC) was used to evaluate the dynamic cumulative performance of the models. The importance of the predictors in the final prediction model was evaluated using the Shapley additive explanations (SHAP) value.RESULTS: On average, the final XGBoost-powered Cox regression model performed at an acceptable level for patients with a length of stay up to 250 days (mean time-dependent AUC = 0.713) in the test dataset. However, for patients with a length of stay between 20 and 213 days, the performance of the model was relatively poor (time-dependent AUC < 0.7). When limited to patients with a length of stay ≤20 days, which accounts for 95.4% of all the patients, the model achieved an excellent performance (mean time-dependent AUC = 0.813). When further limited to patients with a length of stay ≤5 days, which accounts for two-thirds of all the patients, the model achieved an outstanding performance (mean time-dependent AUC = 0.917).CONCLUSION: The XGBoost-powered Cox regression model can achieve an outstanding predictive ability for in-hospital mortality during the first 5 days, primarily based on the severity of the injury, the GCS on admission, and the patient's age. These variables continue to demonstrate an excellent predictive ability up to 20 days after admission, a period of care that accounts for over 95% of severe TBI patients. Past 20 days of care, other factors appear to be the primary drivers of in-hospital mortality, indicating a potential window of opportunity for improving outcomes.
39.	Cao, Yang, Associate Professor, 1972-, et al. (författare) Predicting Long-Term Health-Related Quality of Life after Bariatric Surgery Using a Conventional Neural Network : A Study Based on the Scandinavian Obesity Surgery Registry 2019 Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 8:12 Tidskriftsartikel (refereegranskat)abstract Severe obesity has been associated with numerous comorbidities and reduced health-related quality of life (HRQoL). Although many studies have reported changes in HRQoL after bariatric surgery, few were long-term prospective studies. We examined the performance of the convolution neural network (CNN) for predicting 5-year HRQoL after bariatric surgery based on the available preoperative information from the Scandinavian Obesity Surgery Registry (SOReg). CNN was used to predict the 5-year HRQoL after bariatric surgery in a training dataset and evaluated in a test dataset. In general, performance of the CNN model (measured as mean squared error, MSE) increased with more convolution layer filters, computation units, and epochs, and decreased with a larger batch size. The CNN model showed an overwhelming advantage in predicting all the HRQoL measures. The MSEs of the CNN model for training data were 8% to 80% smaller than those of the linear regression model. When the models were evaluated using the test data, the CNN model performed better than the linear regression model. However, the issue of overfitting was apparent in the CNN model. We concluded that the performance of the CNN is better than the traditional multivariate linear regression model in predicting long-term HRQoL after bariatric surgery; however, the overfitting issue needs to be mitigated using more features or more patients to train the model.
40.	Cao, Yang, Associate Professor, 1972-, et al. (författare) Predictive Values of Preoperative Characteristics for 30-Day Mortality in Traumatic Hip Fracture Patients 2021 Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:5 Tidskriftsartikel (refereegranskat)abstract Hip fracture patients have a high risk of mortality after surgery, with 30-day postoperative rates as high as 10%. This study aimed to explore the predictive ability of preoperative characteristics in traumatic hip fracture patients as they relate to 30-day postoperative mortality using readily available variables in clinical practice. All adult patients who underwent primary emergency hip fracture surgery in Sweden between 2008 and 2017 were included in the analysis. Associations between the possible predictors and 30-day mortality was performed using a multivariate logistic regression (LR) model; the bidirectional stepwise method was used for variable selection. An LR model and convolutional neural network (CNN) were then fitted for prediction. The relative importance of individual predictors was evaluated using the permutation importance and Gini importance. A total of 134,915 traumatic hip fracture patients were included in the study. The CNN and LR models displayed an acceptable predictive ability for predicting 30-day postoperative mortality using a test dataset, displaying an area under the ROC curve (AUC) of as high as 0.76. The variables with the highest importance in prediction were age, sex, hypertension, dementia, American Society of Anesthesiologists (ASA) classification, and the Revised Cardiac Risk Index (RCRI). Both the CNN and LR models achieved an acceptable performance in identifying patients at risk of mortality 30 days after hip fracture surgery. The most important variables for prediction, based on the variables used in the current study are age, hypertension, dementia, sex, ASA classification, and RCRI.
41.	Cao, Yang, Associate Professor, 1972-, et al. (författare) Using a Convolutional Neural Network to Predict Remission of Diabetes After Gastric Bypass Surgery : Machine Learning Study From the Scandinavian Obesity Surgery Register 2021 Ingår i: JMIR Medical Informatics. - : JMIR Publications. - 2291-9694. ; 9:8 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Prediction of diabetes remission is an important topic in the evaluation of patients with type 2 diabetes (T2D) before bariatric surgery. Several high-quality predictive indices are available, but artificial intelligence algorithms offer the potential for higher predictive capability.OBJECTIVE: This study aimed to construct and validate an artificial intelligence prediction model for diabetes remission after Roux-en-Y gastric bypass surgery.METHODS: Patients who underwent surgery from 2007 to 2017 were included in the study, with collection of individual data from the Scandinavian Obesity Surgery Registry (SOReg), the Swedish National Patients Register, the Swedish Prescribed Drugs Register, and Statistics Sweden. A 7-layer convolution neural network (CNN) model was developed using 80% (6446/8057) of patients randomly selected from SOReg and 20% (1611/8057) of patients for external testing. The predictive capability of the CNN model and currently used scores (DiaRem, Ad-DiaRem, DiaBetter, and individualized metabolic surgery) were compared.RESULTS: In total, 8057 patients with T2D were included in the study. At 2 years after surgery, 77.09% achieved pharmacological remission (n=6211), while 63.07% (4004/6348) achieved complete remission. The CNN model showed high accuracy for cessation of antidiabetic drugs and complete remission of T2D after gastric bypass surgery. The area under the receiver operating characteristic curve (AUC) for the CNN model for pharmacological remission was 0.85 (95% CI 0.83-0.86) during validation and 0.83 for the final test, which was 9%-12% better than the traditional predictive indices. The AUC for complete remission was 0.83 (95% CI 0.81-0.85) during validation and 0.82 for the final test, which was 9%-11% better than the traditional predictive indices.CONCLUSIONS: The CNN method had better predictive capability compared to traditional indices for diabetes remission. However, further validation is needed in other countries to evaluate its external generalizability.
42.	Castelo-Branco, Anna, et al. (författare) Infections in patients with multiple sclerosis : A national cohort study in Sweden 2020 Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 45 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Multiple sclerosis (MS) patients have an increased risk of infections, but few population-based studies have reported infections occurring in MS in the years immediately after diagnosis.OBJECTIVE: To explore incident infections in MS, stratified by age and sex.METHODS: In a Swedish population-based cohort study 6602 incident MS patients (aged ≥18 years), matched at diagnosis with 61,828 matched MS-free individuals were identified between 1st January 2008 and 31st December 2016, using national registers. Incidence rates (IR) and incidence rate ratios (IRR) with 95% CI were calculated for each outcome.RESULTS: The IRRs were 2.54 (95% CI 2.28-2.83) for first serious infection and 1.61 (1.52-1.71) for first non-serious infection. Compared with MS-free individuals, MS patients had higher IRs for skin, respiratory/throat infections, pneumonia/influenza, bacterial, viral, and fungal infections, with the highest IRR observed for urinary tract/kidney infections (2.44; 2.24-2.66). The cumulative incidence for most of these infections was higher among MS patients than MS-free individuals, both 0 to <5 and 5 to <9 years after index date.CONCLUSION: The burden of infections around the time of MS diagnosis and subsequent infection risk, underscore the need for careful considerations regarding the risk-benefit across different disease-modifying therapies.
43.	Castelo-Branco, Anna, et al. (författare) Non-infectious comorbidity in patients with multiple sclerosis : A national cohort study in Sweden 2020 Ingår i: Multiple Sclerosis Journal, Experimental, Translational and Clinical. - California, USA : Sage Publications. - 2055-2173. ; , s. 1-10 Tidskriftsartikel (refereegranskat)abstract Background: Comorbidity is of significant concern in multiple sclerosis (MS). Few population-based studies have reported conditions occurring in MS after diagnosis, especially in contemporary cohorts.Objective: To explore incident comorbidity, mortality and hospitalizations in MS, stratified by age and sex.Methods: In a Swedish population-based cohort study 6602 incident MS patients (aged ≥18 years) and 61,828 matched MS-free individuals were identified between 1 January 2008 and 31 December 2016, using national registers. Incidence rates (IRs) and incidence rate ratios (IRRs) with 95% CI were calculated for each outcome.Results: IRs of cardiovascular disease (CVD) were higher among MS patients than MS-free individuals, (major adverse CVD: IRR 1.42; 95% CI 1.12-1.82; hemorrhagic/ischemic stroke: 1.46; 1.05-2.02; transient ischemic attack: 1.65; 1.09-2.50; heart failure: 1.55; 1.15-2.10); venous thromboembolism: 1.42; 1.14-1.77). MS patients also had higher risks of several non-CVDs such as autoimmune conditions (IRR 3.83; 3.01-4.87), bowel dysfunction (2.16; 1.86-2.50), depression (2.38; 2.11-2.68), and fractures (1.32; 1.19-1.47), as well as being hospitalized and to suffer from CVD-related deaths ((1.91; 1.00-3.65), particularly in females (3.57; 1.58-8.06)).Conclusion: MS-patients experience a notable comorbidity burden which emphasizes the need for integrated disease management in order to improve patient care and long-term outcomes of MS.
44.	Castelo-Branco, A., et al. (författare) Treatment patterns in patients with multiple sclerosis : a single hospital cohort study in Sweden 2021 Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:Suppl. 2, s. 732-732 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Introduction: An increasing number of disease-modifying therapies (DMT) for multiple sclerosis (MS) has led to switching between treatments.Objectives: In a Swedish MS cohort study, we analysed switching treatment patterns, including prescribed symptomatic medications, before and after an MS diagnosis.Methods: A national incident MS cohort diagnosed in 2008–2016 in the Swedish National Patient Register was linked to the national Prescribed Drug Register. A subcohort in the electronic medical records (EMR) of the Karolinska University Hospital was analysed for medication usage.Results: Patients with an MS diagnosis in the EMR cohort (n=1289) were identified (female, 68.2%; mean age (standard deviation), 38.8 (12.2) years). Prescribed symptomatic medications in the year before cohort entry included analgesics (23.2%), antidepressants (13.9%), opioids (13.4%), systemic corticosteroids (11.2%), and anxiolytics (10.0%). In the 4 years after cohort entry, medications included analgesics (65.2%), systemic antibacterials (55.9%), anti-inflammatory and antirheumatics (50.1%), antidepressants (34.8%), anxiolytics (21.1%), antiepileptics (19.1%) and ophthalmic drugs (16.6%). Of 1289 patients, 1040 were prescribed a DMT (80.7%). Median time (months, interquartile range) to first usage of new DMTs by age group was 1.71, 0.82–4.30 (<40 years); 1.87, 0.95–7.00 (40–59 years); and 3.96, 1.15–12.16 (⩾60 years). The most common DMTs (n=patients) were first-line (n=1054): interferons (55.9%), rituximab (15.7%), dimethyl fumarate (9.1%), natalizumab (7.4%), glatiramer acetate (7.1%), fingolimod (3.5%); second-line (n=551): rituximab (29.4%), natalizumab (19.4%), dimethyl fumarate (17.6%), fingolimod (16.3%), glatiramer acetate (7.8%), interferons (3.1%), teriflunomide (2.2%); third-line (n=184): rituximab (51.1%), natalizumab (13.0%), interferons (9.8%), fingolimod (9.8%), dimethyl fumarate (6.0%).Conclusions: These data indicate high usage of prescribed symp-tomatic medications before and after the MS diagnosis, which may indicate the consequences of prodromal and early sympto-matic MS. Most patients were treated with a DMT within months of diagnosis, with predominant initial use of interferons, and switching to more potent agents in later lines of therapy. Prescribing patterns are changing and expected to evolve further with earlier use of powerful agents.
45.	Cheng, Helen, et al. (författare) Associations between childhood biomedical factors, maternal smoking, personality traits, Body and Mass Index and the prevalence of asthma in adulthood 2018 Ingår i: Psychology and Health. - : Routledge. - 0887-0446 .- 1476-8321. ; 33:9, s. 1116-1129 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: The study set out to investigate socio-economic, biomedical, health and behavioural and psychological factors in childhood and adulthood associated with the prevalence of asthma in adulthood, drawing data from The National Child Development Studies (NCDS), a birth cohort in the UK.DESIGN: The National Child Development Study, a nationally representative sample of 17,415 babies born in Great Britain in 1958 and followed up at 7, 11, 33 and 50 years was used.MAIN OUTCOME MEASURE: The prevalence of asthma at age 50 was the outcome measure. The analytic sample consists of 5118 participants with complete data on a set of measures at birth, at ages 7, 11, 33 and 50 years.RESULTS: Using logistic regression analyses, results showed that childhood asthma (OR = 6.77: 4.38-10.48, p < .001) and respiratory symptoms (OR = 1.83: 1.18-2.86, p < .01), maternal smoking during pregnancy (OR = 1.26: 1.00-1.59, p < .05), Body and Mass Index (BMI) (OR = 1.03: 1.02-1.05, p < .001), traits Neuroticism (OR = 1.13: 1.01-1.21, p < .05) and Conscientiousness (OR = 0.76: 0.76-0.96, p < .01), as well as sex (OR = 1.49: 1.15-1.94, p < .001) were all significantly associated with the prevalence of asthma in adulthood.CONCLUSION: The study shows that both childhood and adulthood psychological and sociological factors are significantly associated with the prevalence of asthma in adulthood, though more work need to be done in this area.
46.	Cheng, Helen, et al. (författare) Associations between familial factor, trait conscientiousness, gender and the occurrence of type 2 diabetes in adulthood : evidence from a British cohort 2015 Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 10:5 Tidskriftsartikel (refereegranskat)abstract Objective: To investigate social, familial, and psychological factors in influencing the occurrence of type 2 diabetes in adulthood.Method: Some 17,415 babies born in Great Britain in 1958 and followed up at 7, 11, 33, and 50 years of age. The prevalence of type 2 diabetes at age 50 years was the outcome measure.Results: Some 5,032 participants with data on parental social class, childhood cognitive ability tests scores at age 11 years, educational qualifications at age 33 years, personality traits, occupational levels, and type 2 diabetes (all measured at age 50 years) were included in the study. Available information also included whether cohort members' parents or siblings had diabetes. Using logistic regression analyses, results showed that sex (OR= 0.63: 0.42-0.92, p<. 05), family history (OR= 3.40: 1.76-6.55, p<. 01), and trait conscientiousness (OR= 0.76: 0.64-0.90, p<. 001) were all significantly and independently associated with the occurrence of type 2 diabetes in adulthood. It appears that the occurrence of type 2 diabetes is greater among men than women (4.3% vs 2.5%).Conclusion: Familial (genetic and non-genetic) and psychological factors are significantly associated with the prevalence of type 2 diabetes in adulthood.
47.	Cheng, Helen, et al. (författare) Biomedical, psychological, environmental and behavioural factors associated with adult obesity in a nationally representative sample 2020 Ingår i: Journal of Public Health. - : Springer. - 1741-3842 .- 1741-3850. ; 42:3, s. 570-578 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To identify personality, biomedical and behavioural factors associated with adult obesity in a large longitudinal sample.METHOD: In total, 5360 participants with data on personality, neurological functioning, maternal smoking during pregnancy, education and occupation, physical exercise, adult self-reported BMI and obesity were included in the study. Obesity at 55 years was the outcome variable.RESULTS: The rates of obesity increased from 9.5 to 22.8% from age 33 to 55 years. Logistic regression analyses (adjusted estimates) showed that childhood neurological functioning (OR = 1.32: 1.07-1.63, P < 0.01), maternal smoking during pregnancy (OR = 1.42: 1.22-1.65, P < 0.001), educational qualifications (OR = 0.54: 0.37-0.79, P < 0.01), trait conscientiousness (OR = 0.80:0.74-0.86, P < 0.001) and physical exercise (OR = 0.87: 0.82-0.92, P < 0.001) were significant predictors of obesity at age 55 years for both men and women. Trait extraversion for men (OR = 1.16: 1.07-1.26, P < 0.001) and trait emotional stability for women (OR = 0.90: 0.82-0.99, P < 0.05) were also significant predictors of the outcome variable.CONCLUSION: Biomedical, psychological, environmental and behavioural factors were all associated with adult obesity.
48.	Cheng, Helen, et al. (författare) Childhood heart problems, adulthood emotional stability, and sex associated with self-report heart conditions in adulthood 2021 Ingår i: Journal of Health Psychology. - : Sage Publications. - 1359-1053 .- 1461-7277. ; 26:4, s. 489-499 Tidskriftsartikel (refereegranskat)abstract The present study investigated biomedical, social, and psychological factors associated with self-reported heart conditions in adulthood in a British cohort. In total, 5697 (50.7% males) participants with data on parental socioeconomic status, childhood cognitive ability, childhood heart problems, educational qualifications, current occupational levels, adulthood personality traits, and the prevalence of self-reported heart conditions in adulthood were included in the study. The prevalence of self-reported heart conditions measured at age 54 years was the outcome variable. Hierarchical logistic regression analysis showed that childhood heart problems identified by physicians (OR = 3.47:1.74-6.92, p < 0.001) and trait emotional stability (OR = 0.83:0.75-0.93, p < 0.001) were the significant and independent predictors of self-reported heart conditions in adulthood. There were also significant sex effects on the prevalence of the outcome variable (OR = 0.53:0.42-0.63, p < 0.001). Both a biomedical and a psychological factor were significantly associated with self-reported heart conditions in adulthood.
49.	Cheng, Helen, et al. (författare) Emotional stability, conscientiousness, and self-reported hypertension in adulthood 2017 Ingår i: Personality and Individual Differences. - : Elsevier. - 0191-8869 .- 1873-3549. ; 115, s. 159-163 Tidskriftsartikel (refereegranskat)abstract This study aimed to investigate social and psychological factors in childhood and adulthood associated with self-reported hypertension in adulthood. Using data from the National Child Development Study, a nationally representative sample of 17,415 babies born in Great Britain in 1958 and followed up at 11, 33, and 50 years of age. Self-reported diagnosed hypertension by 50 years was the outcome measure. In total, 5753 participants with complete data on parental social class at birth, childhood cognitive ability test scores at 11 years, educational qualifications at 33 years, personality traits, occupational levels, and self-reported hypertension (all measured at age 50 years) were included in the study. Using logistic regression analyses, results showed that sex (OR = 0.60: 0.49–0.73, p < .001), educational qualifications (OR = 0.59: 0.37–0.92, p < .05), and traits emotional stability (OR = 0.84: 0.77–0.91, p < .001) and conscientiousness (OR = 0.89: 0.82–0.98, p < .05) were all significantly associated with the occurrence of self-reported hypertension in adulthood. Both psychological factors and socio-demographic factors were significantly associated with self-reported hypertension in adulthood.
50.	Cheng, Helen, et al. (författare) The associations between personality traits, education, occupation and the occurrence of eczema in adulthood 2017 Ingår i: Journal of Health Psychology. - London, United Kingdom : Sage Publications. - 1359-1053 .- 1461-7277. ; 22:7, s. 916-924 Tidskriftsartikel (refereegranskat)abstract There were 5834 participants with complete data on parental social class at birth, childhood cognitive ability tests scores at 11 years, educational qualifications at 33 years, the Big Five-Factor personality traits, occupational levels and eczema (measured at age 50 years). Results showed that eczema in childhood, educational achievement and occupational levels were significantly associated with the occurrence of reported eczema in adulthood. Emotionally Stable people (non-neurotic) were less likely to have eczema, but those with high Agreeableness and Openness more likely to have eczema. Childhood cognitive ability was significantly and positively associated with eczema in adulthood.

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