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- van de Vegte, Yordi, et al.
(författare)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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| 2. |
- Gadan, Soran, 1976-
(författare)
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Long term aspects of defunctioning stoma following low anterior resection for rectal cancer
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In Sweden, more than 2 000 individuals are diagnosed with rectal cancer each year. Surgery is the main curative treatment, and involves removal of the tumor with the surrounding mesorectum in adefined anatomical plane. Intestinal continuity is restored by anastomosing the colon to the rectalstump at the pelvic floor. Leakage of the anastomosis is a potentially life-threatening complication, and is most common in low anastomoses located at the pelvic floor. A temporary defunctioning loop stoma (DS) reduces both the rate of leakage and the severity when leakage occurs despite DS. The use of DS has increased substantially in Sweden over the last 15 years, especially in low anastomoses at the level of the pelvic floor. The purpose of this thesis was to increase the understanding of different aspects of DS and its impact on anorectal function, long-term survival, cancer recurrence, timing of stoma reversal, and the risk of having a permanent stoma.In Paper I, the LARS score questionnaire was used to assess anorectal function among patients who had participated in a Swedish nationwide randomized trial. Those who had a DS (n=116) were compared to those without DS (n=118). After a median follow-up time of 12 years, patients with DS had a poorer bowel function than those without DS in terms of incontinence for gas and loose stools. No differences were found with regard to fecal incontinence, defragmentation, and urgency. Women and patients who had received preoperative radiotherapy had poorer anorectal function. Impaired anorectal function was associated with lower self-perceived health.In Paper II, a cohort of 110 patients from Örebro Region, Sweden, was investigated with regard to whether or not the DS was reversed within a 4-month period. Only 25% had their stoma reversed within this timeframe. Moreover, a third of the patients had a delayed stoma closure without any identifiable medical reason. This was an improvement compared to a previous study from the same region, which found that 58% of patients operated between 1995 and 2007 had a delayed stoma reversal without any identifiable medical reason. The most common cause for delayed DS reversal in our study was adjuvant chemotherapy (38%).In Paper III, the impact of DS on long-term survival and local and distant cancer recurrence was investigated in a nationwide population-based study cohort operated with low anterior resection (LAR) between 1995 and 2010 (n=4130), retrieved from the Swedish Colorectal Cancer Registry. Patients with a DS at LAR (n=2163) had an increased survival rate during the first 3 years afterindex surgery in comparison with those without a DS. Beyond 3 years of follow-up, no difference was noted between the two groups. There were no differences regarding either local cancer recurrence or distant metastases between patients with and without DS.In Paper IV, the risk of having a permanent stoma beyond 5 years after rectal cancer surgery was evaluated in 232 patients (excluding mortality within 90 days; n=2) previously randomized to DS or no DS. After a median follow-up of 15 years, 25% (57/232) had a permanent stoma. Of these, 23% (13/57) had their permanent stoma constructed at median 10 years after the index surgery. The incidence of permanent stoma was numerically lower in the group originally randomized to DS, but this difference was not statistically significant. Anastomotic leakage was the most common riskfactor for ending up with a permanent stoma.
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| 3. |
- Höglund, Berit, 1955-
(författare)
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Pregnancy, Childbirth and Midwifery Care among Women with Intellectual Disability in Sweden : Epidemiological and Descriptive Studies
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to investigate pregnancy and childbirth in women with intellectual disability (ID), in Sweden, the health of their newborns and midwifery care for these women. Two register studies and two descriptive studies are included. Pregnancy and birth outcomes as well as data on the newborns’ health were examined by linking data from the National Patient Register and the Medical Birth Register (I-II). The women’s experience of pregnancy and delivery was investigated with repeated interviews (III). Midwives’ knowledge of, experience of and attitudes towards pregnancy and childbirth in women with ID were evaluated with questionnaires (IV). Mothers with ID were more often teenagers, smoked more during pregnancy and had more Caesarean Sections. Their children had a higher proportion of pre-term births, were small-for-gestational-age, stillborn or died in the perinatal period. The women with ID struggled to attain motherhood and feared to lose custody of the child. The pregnancy was seen as a happy event, even though relatives did not always approve. Parent education was considered important, but not adequately adapted to their needs. The birth process was overwhelming and difficult to understand, but the child was welcomed with warm feelings, and breastfeeding was natural. Midwives stated it was different to care for women with ID and requested additional knowledge. The majority of midwives affirmed that women with ID could not manage the mother role satisfactorily, and one-third expressed that women with ID should refrain from having children. A majority of the midwives considered that the children should grow up with the parents with support from family and society, but one out of five stated that the children should grow up in foster care.Conclusion: Women with ID and their children should be considered as risk groups in pregnancy and childbirth. Professionals in maternity services need to elucidate their knowledge and skills for counselling and supporting this particular group of pregnant women in pre-, intra- and post-partum care.
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| 4. |
- Wildeman, Peter, 1975-
(författare)
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Prosthetic Joint Infection of the Hip : Cause and Effect
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Every year, 18 000 patients in Sweden and more than 1 million worldwide undergo total hip arthroplasty (THA). The operation is of great benefit to patients, but is associated with several complications. Prosthetic joint infections (PJIs) are among the most common complications, and can be devastating in terms of suffering for the patient and cost for the healthcare provider. The aim of this thesis was to investigate different aspects of PJIs in order to gain a better understanding of the causes and effects of infection. Four studies were conducted covering genomic analysis of the causative organism, identification of risk factors for failure of treatment, evaluation of a national infection control program aimed at reducing the burden of infections (PRISS: Prosthesis-related infections shall be stopped), and examination of the long-term impact of a PJI on the patient’s health through patient-reported measurement questionnaires.The main findings were as follows. Commensal bacteria such as Cutibacterium avidum have the potential to cause PJIs, and should be specially accounted for when performing hip surgery with an anterior approach. S. aureus is both a commensal and a pathogen with invasive capacity, and the commensal strains do not differ from the PJI strains regarding prevalence of virulence genes and clonal complexes. The genomic traits of pathogens had no impact on treatment success or eradication of infection in S. aureus PJIs The long-term effects of a PJI in the hip include increased mortality, lower quality of life, and decreased hip function. The incidence of PJIs was higher following the PRISS project. Increasing risk factors contributing to PJI explain the increasing incidence of PJI after primary THA.In conclusion, PJIs of the hip have multifactorial causes which are difficult to reduce, and long-term effects are severe.
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