| 1. |
- Lebwohl, Benjamin, et al.
(författare)
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Celiac disease and non-celiac gluten sensitivity
- 2015
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Ingår i: BMJ-BRITISH MEDICAL JOURNAL. - : B M J Group. - 1756-1833. ; 351
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Forskningsöversikt (refereegranskat)abstract
- Celiac disease is a multisystem immune based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The prevalence of celiac disease has risen in recent decades and is currently about 1% in most Western populations. The reason for this rise is unknown, although environmental factors related to the hygiene hypothesis are suspected. The pathophysiology of celiac disease involves both the innate and adaptive immune response to dietary gluten. Clinical features are diverse and include gastrointestinal symptoms, metabolic bone disease, infertility, and many other manifestations. Although a gluten-free diet is effective in most patients, this diet can be burdensome and can limit quality of life; consequently, non-dietary therapies are at various stages of development. This review also covers non-celiac gluten sensitivity. The pathophysiology of this clinical phenotype is poorly understood, but it is a cause of increasing interest in gluten-free diets in the general population.
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| 2. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
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Maternal vaccination against H1N1 influenza and offspring mortality : population based cohort study and sibling design
- 2015
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Ingår i: BMJ. British Medical Journal. - London, United Kingdom : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 351
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Tidskriftsartikel (refereegranskat)abstract
- Study question: What is the mortality in offspring of mothers who hadinfluenza A(H1N1)pdm09 vaccination during pregnancy?Methods: This was a prospective population based cohort study in seven healthcare regions in Sweden based on vaccinations taking place between 2 October 2009 and 26 November 2010. H1N1 vaccination data were linked with pregnancy and birth characteristics and offspring mortality data in 275 500 births (of which 1203 were stillbirths) from 137 886 mothers. Of these offspring, 41 183 had been exposed to vaccination with Pandemrix, a monovalent AS03 adjuvanted H1N1 influenza vaccine, during fetal life. A primary comparison group consisted of pregnancies of women who were not vaccinated during the same calendar period. In a second comparison, non-exposed siblings of infants prenatally exposed to vaccination were used as controls. Cox regression was used to estimate hazard ratios for stillbirth, early neonatal mortality (days 0-6 after birth), and subsequent mortality (beginning on day 7) in vaccinated versus nonvaccinated women, adjusting for mother’s age at delivery, body mass index, parity, smoking, country of birth, and disposable income and for sex of offspring.Study answer and limitations: The results of this study suggest that AS03 adjuvanted H1N1 vaccination during pregnancy does not affect the risk of stillbirth, early neonatal death, or later mortality in the offspring. During follow-up, 1172 stillbirths, 380 early neonatal deaths, and 706 deaths thereafter occurred. Compared with general population controls, this corresponded to adjusted hazard ratios of 0.83 (95% confidence interval 0.65 to 1.04) for stillbirth, 0.71 (0.44 to 1.14) for early neonatal death, and 0.97 (0.69 to 1.36) for later death. When siblings were used as controls, adjusted hazard ratios were 0.88 (0.59 to 1.30) for stillbirth, 0.82 (0.46 to 1.49) for early neonatal death, and 0.78 (0.52 to 1.19) for later death. Limitations of the study include lack of data on miscarriage before gestational week 22, inability to ascertain which mothers had pandemic flu during pregnancy, and lack of data on factors influencing the decision to vaccinate during pregnancy.What this study adds: H1N1 vaccination during pregnancy is not associated with adverse fetal outcome or offspring mortality, including when familial factors are taken into account.
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| 3. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
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Periconception glycaemic control in women with type 1 diabetes and risk of major birth defects: population based cohort study in Sweden
- 2018
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833 .- 0959-8138. ; 362
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To examine the association between maternal type 1 diabetes and the risk of major birth defects according to levels of glycated haemoglobin (HbA1C) within three months before or after estimated conception. Population based historical cohort study using nationwide health registers. 2458 singleton liveborn infants of mothers with type 1 diabetes and a glycated haemoglobin measurement within three months before or after estimated conception and 1 159 865 infants of mothers without diabetes. Major cardiac and non-cardiac birth defects according to glycated haemoglobin levels. 122 cases of major cardiac defects were observed among 2458 infants of mothers with type 1 diabetes. Compared with 15 cases of major cardiac defects per 1000 infants of mothers without diabetes, the rates among infants of mothers with type 1 diabetes were 33 per 1000 for a glycated haemoglobin level of <6.5% (adjusted risk ratio 2.17, 95% confidence interval 1.37 to 3.42), 49 per 1000 for 6.5% to <7.8% (3.17, 2.45 to 4.11), 44 per 1000 for 7.8% to <9.1% (2.79, 1.90 to 4.12), and 101 per 1000 for >= 9.1% (6.23, 4.32 to 9.00). The corresponding adjusted risk differences were 17 (5 to 36), 32 (21 to 46), 26 (13 to 46), and 77 (49 to 118) cases of major cardiac defects per 1000 infants, respectively. 50 cases of major non-cardiac defects were observed among infants of mothers with type 1 diabetes. Compared with 18 cases of major non-cardiac defects per 1000 infants of mothers without diabetes, the rates among infants of mothers with type 1 diabetes were 22 per 1000 for a glycated haemoglobin level of <6.5% (adjusted risk ratio 1.18, 0.68 to 2.07), 19 per 1000 for 6.5% to <7.8% (1.01, 0.66 to 1.54), 17 per 1000 for 7.8% to <9.1% (0.89, 0.46 to 1.69), and 32 per 1000 for >= 9.1%(1.68, 0.85 to 3.33). Among liveborn infants of mothers with type 1 diabetes, increasingly worse glycaemic control in the three months before or after estimated conception was associated with a progressively increased risk of major cardiac defects. Even with glycated haemoglobin within target levels recommended by guidelines (<6.5%), the risk of major cardiac defects was increased more than twofold. The risk of major non-cardiac defects was not statistically significantly increased at any of the four glycated haemoglobin levels examined; the study had limited statistical power for this outcome and was based on live births only.
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| 4. |
- Olén, Ola, et al.
(författare)
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Childhood onset inflammatory bowel disease and risk of cancer : a Swedish nationwide cohort study 1964-2014
- 2017
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Ingår i: BMJ-BRITISH MEDICAL JOURNAL. - : B M J Group. - 1756-1833. ; 11:Suppl. 1, s. S14-S15
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess risk of cancer in patients with childhood onset inflammatory bowel disease in childhood and adulthood.Design: Cohort study with matched general population reference individuals using multivariable Cox regression to estimate hazard ratios.Setting: Swedish national patient register (both inpatient and non-primary outpatient care) 1964-2014.Participants: Incident cases of childhood onset (<18 years) inflammatory bowel disease (n=9405: ulcerative colitis, n=4648; Crohn's disease, n=3768; unclassified, n=989) compared with 92 870 comparators from the general population matched for sex, age, birth year, and county.Main outcome measures: Any cancer and cancer types according to the Swedish Cancer Register.Results: During follow-up through adulthood (median age at end of follow-up 27 years), 497 (3.3 per 1000 person years) people with childhood onset inflammatory bowel disease had first cancers, compared with 2256 (1.5 per 1000 person years) in the general population comparators (hazard ratio 2.2, 95% confidence interval 2.0 to 2.5). Hazard ratios for any cancer were 2.6 in ulcerative colitis (2.3 to 3.0) and 1.7 in Crohn's disease (1.5 to 2.1). Patients also had an increased risk of cancer before their 18th birthday (2.7, 1.6 to 4.4; 20 cancers in 9405 patients, 0.6 per1000 person years). Gastrointestinal cancers had the highest relative risks, with a hazard ratio of 18.0 (14.4 to 22.7) corresponding to 202 cancers in patients with inflammatory bowel disease. The increased risk of cancer (before 25th birthday) was similar over time (1964-1989: 1.6, 1.0 to 2.4; 1990-2001: 2.3, 1.5 to 3.3); 2002-06: 2.9, 1.9 to 4.2; 2007-14: 2.2, 1.1 to 4.2).Conclusion: Childhood onset inflammatory bowel disease is associated with an increased risk of any cancer, especially gastrointestinal cancers, both in childhood and later in life. The higher risk of cancer has not fallen over time.
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| 5. |
- Song, Mingyang, et al.
(författare)
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Risk of colorectal cancer in first degree relatives of patients with colorectal polyps : nationwide case-control study in Sweden
- 2021
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 373
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the risk of colorectal cancer (CRC) in first degree relatives (parents and full siblings) of patients with precursor lesions (polyps) for CRC.DESIGN: Case-control study.SETTING: Linkage to the multi-generation register and gastrointestinal ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) histopathology cohort in Sweden.PARTICIPANTS: 68 060 patients with CRC and 333 753 matched controls.MAIN OUTCOME MEASURES: Multivariable adjusted odds ratios of CRC according to the number of first degree relatives with a colorectal polyp and the histology of polyps and age at diagnosis in first degree relatives. Subgroup analysis was also performed according to age at CRC diagnosis and evaluated the joint association of family history of colorectal polyps and family history of CRC.RESULTS: After adjusting for family history of CRC and other covariates, having a first degree relative with a colorectal polyp (8.4% (5742/68 060) in cases and 5.7% (18 860/333 753) in controls) was associated with a higher risk of CRC (odds ratio 1.40, 95% confidence interval 1.35 to 1.45). The odds ratios ranged from 1.23 for those with hyperplastic polyps to 1.44 for those with tubulovillous adenomas. To better put this risk in perspective, the age specific absolute risk of colon and rectal cancers was estimated according to family history of polyps based on the 2018 national CRC incidence in Sweden. For example, the absolute risk of colon cancer in individuals aged 60-64 years with and without a family history of colorectal polyp was, respectively, 94.3 and 67.9 per 100 000 for men and 89.1 and 64.1 per 100 000 for women. The association between family history of polyps and CRC risk was strengthened by the increasing number of first degree relatives with polyps (≥2 first degree relatives: 1.70, 1.52 to 1.90, P<0.001 for trend) and decreasing age at polyp diagnosis (<50 years: 1.77, 1.57 to 1.99, P<0.001 for trend). A particularly strong association was found for early onset CRC diagnosed before age 50 years (≥2 first degree relatives: 3.34, 2.05 to 5.43, P=0.002 for heterogeneity by age of CRC diagnosis). In the joint analysis, the odds ratio of CRC for individuals with two or more first degree relatives with polyps but no CRC was 1.79 (1.52 to 2.10), with one first degree relative with CRC but no polyps was 1.70 (1.65 to 1.76), and with two or more first degree relatives with both polyps and CRC was 5.00 (3.77 to 6.63) (P<0.001 for interaction).CONCLUSIONS: After adjusting for family history of CRC, the siblings and children of patients with colorectal polyps are still at higher risk of CRC, particularly early onset CRC. Early screening for CRC might be considered for first degree relatives of patients with polyps.
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| 6. |
- Sultan, Alyshah Abdul, et al.
(författare)
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Development and validation of risk prediction model for venous thromboembolism in postpartum women : multinational cohort study
- 2016
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Ingår i: BMJ-BRITISH MEDICAL JOURNAL. - London, United Kingdom : B M J Group. - 1756-1833. ; 355
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To develop and validate a risk prediction model for venous thromboembolism in the first six weeks after delivery (early postpartum).DESIGN: Cohort study.SETTING: Records from England based Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) and data from Sweden based registry.PARTICIPANTS: All pregnant women registered with CPRD-HES linked data between 1997 and 2014 and Swedish medical birth registry between 2005 and 2011 with postpartum follow-up.MAIN OUTCOME MEASURE: Multivariable logistic regression analysis was used to develop a risk prediction model for postpartum venous thromboembolism based on the English data, which was externally validated in the Swedish data.RESULTS: 433 353 deliveries were identified in the English cohort and 662 387 in the Swedish cohort. The absolute rate of venous thromboembolism was 7.2 per 10 000 deliveries in the English cohort and 7.9 per 10 000 in the Swedish cohort. Emergency caesarean delivery, stillbirth, varicose veins, pre-eclampsia/eclampsia, postpartum infection, and comorbidities were the strongest predictors of venous thromboembolism in the final multivariable model. Discrimination of the model was similar in both cohorts, with a C statistic above 0.70, with excellent calibration of observed and predicted risks. The model identified more venous thromboembolism events than the existing national English (sensitivity 68% v 63%) and Swedish guidelines (30% v 21%) at similar thresholds.CONCLUSION: A new prediction model that quantifies absolute risk of postpartum venous thromboembolism has been developed and externally validated. It is based on clinical variables that are available in many developed countries at the point of delivery and could serve as the basis for real time decisions on obstetric thromboprophylaxis.
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| 7. |
- Ueda, Peter, et al.
(författare)
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Alcohol related disorders among elite male football players in Sweden : nationwide cohort study
- 2022
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Ingår i: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 379
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To assess whether male elite football players are at increased risk of alcohol related disorders compared with men from the general population, and whether such an increased risk would vary on the basis of calendar year of the first playing season in the top tier of competition, age, career length, and goal scoring abilities.DESIGN: Nationwide cohort study.SETTING: Sweden, 1924-2020.PARTICIPANTS: 6007 male football players who had played in the Swedish top division, Allsvenskan, from 1924 to 2019 and 56 168 men from the general population matched to players based on age and region of residence.MAIN OUTCOME MEASURES: Primary outcome was alcohol related disorders (diagnoses recorded in death certificates, during hospital admissions and outpatient visits, or use of prescription drugs for alcohol addiction); secondary outcome was disorders related to misuse of other drugs.RESULTS: During follow-up up to 31 December 2020, 257 (4.3%) football players and 3528 (6.3%) men from the general population received diagnoses of alcohol related disorders. In analyses accounting for age, region of residence, and calendar time, risk of alcohol related disorders was lower among football players than among men from the general population (hazard ratio 0.71, 95% confidence interval 0.62 to 0.81). A reduced risk of alcohol related disorders was observed for football players who played their first season in the top tier in the early 1960s and later, while no significant difference versus men from the general population was seen in the risk for football players from earlier eras. The hazard ratio was lowest at around age 35 years, and then increased with age; at around age 75 years, football players had a higher risk of alcohol related disorders than men from the general population. No significant association was seen between goal scoring, number of games, and seasons played in the top tier and the risk of alcohol related disorders. Risk of disorders related to other drug misuse was significantly lower among football players than the general population (hazard ratio 0.22, 95% confidence interval 0.15 to 0.34).CONCLUSIONS: In this nationwide cohort study, male football players who had played in the Swedish top tier of competition had a significantly lower risk of alcohol related disorders than men from the general population.
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| 8. |
- Örtqvist, Anne K, et al.
(författare)
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Antibiotics in fetal and early life and subsequent childhood asthma : nationwide population based study with sibling analysis
- 2014
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Ingår i: BMJ. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0959-535X .- 1756-1833.
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Tidskriftsartikel (refereegranskat)abstract
- Erratum to this article in BMJ. 2014;349:g7395. OBJECTIVE: To investigate the association between exposure to antibiotics in fetal and early life and asthma in childhood, with adjustment for confounding factors. DESIGN: Nationwide prospective population based cohort study, including sibling control design. SETTING: Swedish population identified from national demographic and health registers. PARTICIPANTS: 493,785 children born 2006-10; 180,894 of these were eligible for sibling analyses. MAIN OUTCOME MEASURE: Asthma defined as having both an asthma diagnosis and dispensed asthma drugs. The association between antibiotic exposure and asthma was investigated in the whole cohort with Cox proportional hazard regression. A stratified proportional hazards model conditional on sibling group was used to adjust for shared factors within families. Confounding by respiratory infections was assessed by investigating whether specific groups of antibiotics were associated with asthma. RESULTS: Antibiotic exposure in fetal life was associated with an increased risk of asthma in cohort analyses (hazard ratio 1.28, 95% confidence interval 1.25 to 1.32), but not in sibling analyses (0.99, 0.92 to 1.07). In cohort analyses, antibiotics used to treat respiratory infections in childhood were associated with a more pronounced increased risk of asthma (4.12, 3.78 to 4.50) than antibiotics used for urinary tract and skin infections (1.54, 1.24 to 1.92). In sibling analyses, the excess risks after exposure to antibiotics for respiratory infections decreased (2.36, 1.78 to 3.13) and disappeared for antibiotics for urinary tract and skin (0.85, 0.47 to 1.55). CONCLUSIONS: Previous positive associations between exposure to antibiotics in fetal and early life and subsequent childhood asthma could have been caused by confounding by shared familial factors, in addition to confounding by respiratory infections.
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