1. |
- Cao, Yang, Associate Professor, 1972-, et al.
(författare)
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The statistical importance of P-POSSUM scores for predicting mortality after emergency laparotomy in geriatric patients
- 2020
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Ingår i: BMC Medical Informatics and Decision Making. - : BioMed Central. - 1472-6947. ; 20:1
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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.
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3. |
- Al Dabbagh, Z., et al.
(författare)
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Long-term pattern of opioid prescriptions after femoral shaft fractures
- 2016
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Ingår i: Acta Anaesthesiologica Scandinavica. - Hoboken, USA : Wiley-Blackwell. - 0001-5172 .- 1399-6576. ; 60:5, s. 634-641
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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.
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4. |
- Al Dabbagh, Zewar, et al.
(författare)
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No signs of dose escalations of potent opioids prescribed after tibial shaft fractures : a study of Swedish National Registries
- 2014
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Ingår i: BMC Anesthesiology. - London : BioMed Central. - 1471-2253 .- 1471-2253. ; 14, s. 4-
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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.
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5. |
- Athlin, Åsa, 1971-, et al.
(författare)
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Diagnostic spirometry in COPD is increasing, a comparison of two Swedish cohorts
- 2023
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Ingår i: npj Primary Care Respiratory Medicine. - : Nature Publishing Group. - 2055-1010. ; 33:1
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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.
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6. |
- Athlin, Åsa, 1971-, et al.
(författare)
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Prediction of Mortality Using Different COPD Risk Assessments : A 12-Year Follow-Up
- 2021
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - : Dove Medical Press Ltd.. - 1176-9106 .- 1178-2005. ; 16, s. 665-675
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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.
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7. |
- Batyrbekova, Nurgul, et al.
(författare)
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Hepatitis C virus infection and the temporal trends in the risk of liver cancer : a national register-based cohort study in Sweden
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:1, s. 63-70
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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.
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8. |
- Bécares, Laia, et al.
(författare)
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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
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Ingår i: Longitudinal and Life Course Studies. - London, England : Society for Longitudinal and Life Course Studies. - 1757-9597. ; 7:1, s. 41-52
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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.
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9. |
- Bejerot, Susanne, 1955-, et al.
(författare)
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Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits)
- 2023
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Ingår i: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 23:1
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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.
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10. |
- Bergh, Cecilia, 1972-, et al.
(författare)
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Determinants in adolescence of stroke-related hospital stay duration in men : a national cohort study
- 2016
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Ingår i: Stroke. - Philadelphia, USA : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 47:9, s. 2416-2418
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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.
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11. |
- Bergh, Cecilia, 1972-, et al.
(författare)
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Non-psychotic mental disorders in adolescent men and risk of myocardial infarction : A national cohort study
- 2020
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 41:Suppl. 2, s. 2812-2812
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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.
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13. |
- Bergh, Cecilia, 1972-, et al.
(författare)
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Severe infections and subsequent delayed cardiovascular disease
- 2017
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Ingår i: European Journal of Preventive Cardiology. - : Sage Publications. - 2047-4873 .- 2047-4881. ; 24:18, s. 1958-1966
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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.
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15. |
- Bergh, Cecilia, 1972-, et al.
(författare)
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Shared unmeasured characteristics among siblings confound the association of Apgar score with stress resilience in adolescence
- 2019
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Ingår i: Acta Paediatrica. - : Wiley-Blackwell Publishing Inc.. - 0803-5253 .- 1651-2227. ; 108:11, s. 2001-2007
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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.
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16. |
- Bergh, Cecilia, 1972-, et al.
(författare)
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Stress resilience and physical fitness in adolescence and risk of coronary heart disease in middle age
- 2015
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Ingår i: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 101:8, s. 623-629
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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.
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17. |
- Bergh, Cecilia, 1972-, et al.
(författare)
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Stress resilience in male adolescents and subsequent stroke risk : cohort study
- 2014
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 85:12, s. 1331-1336
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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.
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18. |
- Bergsten, Elisabet, et al.
(författare)
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Confirmed efficacy of etoposide and dexamethasone in HLH treatment : long-term results of the cooperative HLH-2004 study
- 2017
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 130:25, s. 2728-2738
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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.
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19. |
- Björk, Tabita, 1966-, et al.
(författare)
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Laterality, hand control and scholastic performance : a British birth cohort study
- 2012
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Ingår i: BMJ Open. - London, United Kingdom : BMJ. - 2044-6055. ; 2:2, s. e000314-
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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.
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20. |
- Bouhuis, Dennis, et al.
(författare)
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Factors associated with self-assessed asthma severity
- 2022
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Ingår i: Journal of Asthma. - : Marcel Dekker. - 0277-0903 .- 1532-4303. ; 59:4, s. 691-696
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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.
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21. |
- Bouhuis, Dennis, et al.
(författare)
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Factors Associated with the Non-Exacerbator Phenotype of Chronic Obstructive Pulmonary Disease
- 2023
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - : Dove Medical Press Ltd.. - 1176-9106 .- 1178-2005. ; 18, s. 483-492
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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.
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22. |
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23. |
- Brand, Judith, 1984-, et al.
(författare)
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Association Between Hypertensive Disorders of Pregnancy and Neurodevelopmental Outcomes Among Offspring
- 2021
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Ingår i: JAMA pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 175:6, s. 577-585
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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.
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24. |
- Brand, Judith, 1984-, et al.
(författare)
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Maternal smoking during pregnancy and fractures in offspring : national register based sibling comparison study
- 2020
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 368
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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.
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25. |
- Brand, Judith S, et al.
(författare)
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Risk of serious infections in multiple sclerosis patients by disease course and disability status : Results from a Swedish register-based study
- 2022
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Ingår i: Brain, behavior, & immunity - health. - : Elsevier. - 2666-3546. ; 22
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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.
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