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- Claesson Lingehall, Helena, 1965-
(author)
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Delirium in older people after cardiac surgery : risk factors, dementia, patients’ experiences and assessments
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Background:Delirium is common in older people undergoing cardiac surgery. Delirium is an acute or subacute neuro-psychiatric syndrome, characterized by a change in cognition, disturbances in consciousness; it fluctuates, develops over a short period of time and always has an underlying cause. It is associated with a disturbance in psychomotor activity, and is classified according to different clinical profiles such as hypoactive, hyperactive and mixed delirium. Delirium after cardiac surgery is not harmless, it increases the risk of complications such as prolonged stay in hospital, falls, reduced quality of life, reduced cognitive function and increased mortality.Aim:The overall aim of this thesis was to investigate postoperative delirium in older people undergoing cardiac surgery with Cardiopulmonary Bypass (CPB), focusing on risk factors, dementia and patients’ experiences; and to evaluate an assessment for screening delirium.Methods:This thesis compromises four studies. All participants (n=142) were scheduled for cardiac surgery with use of CPB at the Cardiothoracic Surgery Department, Heart Centre, Umeå University Hospital, Sweden, between February and October 2009. Six structured interviews were conducted preoperatively, day one and day four postoperatively, and in home visits, one, three and five years after surgery (2010, 2012 and 2014). The assessment scales used in Studies I, II and IV were: the Mini-Mental State Examination (MMSE) for cognition, the Organic Brain Syndrome Scale (OBS) for delirium, Geriatric Depression Scale 15 (GDS-15) for depression, Katz staircase with Activities of Daily Living (ADL) for participants’ functional status and the Numerical Rating Scale (NRS) for pain. During the hospital stay, nursing staff used the Swedish version of the Nursing Delirium Screening Scale (Nu-DESC) to assess delirium. Semi-structured interviews were also carried out (III) in the one-year follow up. Delirium, dementia and depression were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM IV TR).Results: Out of 142 participants 54.9% (78/142) developed delirium after cardiac surgery (I). Independent risk factors, predisposing and precipitating, associated with delirium were: age, diabetes, gastritis/peptic ulcer, volume load during operation, longer time on ventilator in intensive care, increased temperature and plasma sodium concentration in the intensive care unit. Out of 114 participants thirty (26.3%) developed dementia within the five years of follow-up. It was shown that a lower preoperative MMSE score and postoperative delirium were factors independently associated with development of dementia (II). One year after cardiac surgery, participants diagnosed with postoperative delirium described in detail feelings of extreme vulnerability and frailty. Despite this, the participants were grateful for the care they had received (III). Hypoactive was the most common symptom profile for delirium. The Swedish version of Nu-DESC showed high sensitivity in detecting hyperactive delirium, but low sensitivity in detecting hypoactive delirium (IV).Conclusion:Delirium was common among older patients undergoing cardiac surgery. Both predisposing and precipitating factors contributed to postoperative delirium. Preventive strategies should be considered in future randomized studies. It might also be suggested that cognitive function should be screened for preoperatively and patients who develop delirium should be followed up to enable early detection of symptoms of dementia. Whether prevention of postoperative delirium can reduce the risk of future dementia remains to be studied. To minimise unnecessary suffering, patients and next of kin should be informed about and prepared for the risk of delirium developing during hospitalization. The Swedish version of Nu-DESC should be combined with cognitive testing to improve detection of hypoactive delirium, but further research is needed. Healthcare professionals need knowledge concerning postoperative delirium in order to prevent, detect and treat delirium so as to avoid and relieve the suffering it might cause.
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| 2. |
- Hedberg, Magnus, 1981-
(author)
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Stroke during cardiac surgery : risk factors, mechanisms and survival effects
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Introduction: Neurological complications and stroke in association with cardiac surgery is a serious problem. The stroke event can occur during surgery (early stroke) or in the postoperative period with a symptom free interval (delayed stroke). Particle embolization due to aortic manipulation during surgery has been suspected as a mechanism for early stroke. The present thesis address mechanisms and survival effects of stroke both clinically (I-III) and experimentally (IV-V). Methods: Study I) Within a cohort of 2641 consecutive cases, a group of cardiac surgery patients with stroke and evaluated by computed tomography (CT) were studied (n=77). CT-findings were analyzed in relation to stroke symptoms. Study II) Data from 9122 patients undergoing coronary surgery were analyzed. Records of patients with any signs of neurological complications were reviewed to extract 149 subjects with stroke at extubation (early, 1.6%) versus 99 patients having a free interval (delayed, 1.1%). Early and delayed stroke were evaluated separately. Independent risk factors for stroke were analyzed by logistic regression and survival by Cox regression (9.3 years median follow-up). Study III) Patients with early (n=223) and delayed stroke (n=116) were identified among 10809 patients undergoing cardiac and aortic surgery, both groups exposed to cardiopulmonary bypass. Stroke patients were subdivided by the hemispheric location of lesions. Subgroups were compared and their associated pre- and peroperative variables and survival were analyzed. Study IV) Aortic cross-clamp manipulation was studied in a human cadaveric perfusion model. The pressurized aorta was repeatedly cross-clamped and washout samples were collected before and after clamp maneuvers. Particles in the washout samples were evaluated by microscopy and by digital image analysis. Study V) Pig aortas were pressurized and cannulated. Washout samples were collected before and after cannulation (n = 40). Particles were deposited onto a 10-μm filter to be evaluated by microscopy and digital image analysis. Results: Study I) In the group of patients exposed to routine cardiac surgery (i.e., clamping and cannulation) and with early stroke, right-hemispheric lesions were more frequent than of the contra-lateral side (P=0.005). Patients with aortic dissections had a strong dominance of bilateral findings, which was different from the unilateral pattern in the routine-surgery group (P<0.001). Study II) Early and delayed stroke did not share any risk factors. Both early and delayed stroke explained mortality in the early postoperative period (P<0.001, P<0.001 respectively) but also at long term follow-up (P=0.008, P<0.001 respectively). For patients surviving their first postoperative year, delayed but not early stroke influenced long-term mortality (P=0.001 and P=0.695, respectively). Study III) Stroke lesions in association to cardiac surgery were near exclusively ischemic. Early stroke had a preponderance for right-hemispheric lesions (P=0.009). In contrast, patients with early stroke that had undergone surgery of the aorta with circulatory arrest showed a pattern with more bilateral lesions compared to ‘cardiac-type’ operations (P<0.001). Patients with bilateral lesions had a dramatically impaired survival compared to those with unilateral lesions (P<0.001). Study IV) In the cadaveric perfusion model, cross-clamping produced a significant output of particles, which was seen for size intervals of 1 mm and smaller (P=0.002 to P=0.022). In all size intervals the particle output correlated with the degree of overall aortic calcification (P =0.002 to P=0.025). Study V) At cannulation of the pig aorta, more particles were noted after cannulation compared to before the maneuver (P<0.001). This increase included small (<0.1 mm, P<0.001) and intermediate-size particles (0.1-0.5 mm, P< 0.001). Particles above 0.5 mm were few and were not associated with cannulation. Conclusions: The influence of stroke on mortality was devastating, for both early and delayed stroke. These two stroke groups had obvious differences in both their risk factors and their hemispheric distribution. It is here emphasized that early and delayed stroke should be considered as two separate entities with suggested mechanistic differences. Ischemic lesions accounted for near all stroke events seen in association to cardiac surgery. For early stroke, these were mostly located within the right hemisphere. Results from the experimental studies underscore microembolic risks associated with aortic manipulation.
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| 3. |
- Smulter, Nina, 1972-
(author)
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Delirium after cardiac surgery : risk factors, assessment methods and costs
- 2018
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Doctoral thesis (other academic/artistic)abstract
- Background: Cardiac surgery is considered safe, but postoperative delirium (POD) remains frequently reported. Delirium is characterised by fluctuations in consciousness and cognition, and can be subdivided into disturbed psychomotoric activity (hyperactive and hypoactive) and psychiatric symptom profiles (psychotic and emotional). Delirium has an underlying cause that can be prevented and treated, provided the condition is detected. Undetected delirium could lead to serious consequences for the patient.Aim: This thesis aims to understand the underlying risk factors of delirium, to compare different assessment methods and documentation, and to understand its effects on hospitalisation costs after cardiac surgery.Methods: Two cohorts of patients undergoing cardiac surgery at the Heart Centre, Umeå University Hospital, Sweden were analysed. Cohort-A (Studies I-IV) enrolled 142 patients, ≥70 years of age, scheduled in 2009 for surgery with cardiopulmonary bypass (CPB). POD was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th ed, text rev (DSM-IV-TR), based on repetitive assessments with the Mini-Mental State Examination (MMSE) and the Organic Brain Syndrome (OBS) scale. This method was considered as reference. Predisposing and precipitating risk factors were explored (Study I), and a separate analysis was conducted with focus on CPB parameters (Study II). Patients were also assessed for POD with the Confusion Assessment Method (CAM), which was validated versus the reference method (Study III). Additionally in Study IV, data about how nurses assessed patients for POD symptoms using the Nursing Delirium Screening Scale (Nu-DESC) were analysed together with information extracted from the clinical database. Moreover, discharge summaries from both nurses and physicians were retrospectively reviewed for key words and expression associated with delirium. Cohort-B (Study V) included 1879 routine cardiac surgery patients (2014-2017) retrospectively extracted from the clinical database with concomitant Nu-DESC scoring. The association between the Nu-DESC and postoperative hospitalization costs was analysed.Results: In cohort-A, 54.9% (78/142) patients developed POD. Both predisposing and precipitating risk factors were significantly associated with POD, of which the ‘volume load during operation’ had the strongest predictive influence (Study I). Among CPB variables the ‘duration of mixed-venous oxygen saturation <75%’ predicted POD (Study II). Hypoactive was more common than hyperactive delirium. Those with hypoactive delirium were less likely to be detected by the CAM method (Study III), an observation also demonstrated from information found in the clinical database and in discharge summaries. Nu-DESC did not detect all patients with POD, but significantly increased the detection rate (Study IV). The major hospitalisation costs associated with Nu-DESC ≥2 occurred in the ICU and independently of the surgical procedure performed. There were no significant differences in costs among patients with Nu-DESC ≥2, between age groups (70-year cut-off) or genders (Study V).Conclusions: Both predisposing and precipitating risk factors contributed to POD and should be considered in future guidelines to prevent delirium after cardiac surgery. Hypoactive delirium was most common, but was the most difficult to detect without screening scales. Systematic assessment with Nu-DESC improved the detection rate of POD. Delirium after cardiac surgery has consequences on healthcare and is associated with increased costs.
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| 4. |
- Sundström, Johan, Professor, 1971-, et al.
(author)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
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In: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
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Journal article (peer-reviewed)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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| 5. |
- Folkersen, Lasse, et al.
(author)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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In: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Journal article (peer-reviewed)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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