| 10351. |
- Oliver, K R, et al.
(författare)
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Immunohistochemical localization of calcitonin receptor-like receptor and receptor activity-modifying proteins in the human cerebral vasculature
- 2002
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016 .- 0271-678X. ; 22:5, s. 620-629
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Tidskriftsartikel (refereegranskat)abstract
- Calcitonin gene-related peptide and adrenomedullin belong to a structurally related neuropeptide family and are potent vasodilators expressed in the trigeminovascular system. The molecular identity of receptors for these proteins has only recently been elucidated. Central to functional binding of these neuropeptides is the G-protein-coupled receptor, the calcitonin receptor-like receptor (CRLR), Whose cell surface expression and pharmacology is determined by coexpression of a receptor activity-modifying protein (RAMP). CRLR combined with RAMP1 binds calcitonin gene-related peptide With high affinity. whereas CRLR coexpression with RAMP2 or -3 confers, high-affinity binding of adrenomedullin. The authors investigated the expression of these receptor components in human cerebral vasculature to further characterize neuropeptide receptor content and the potential functions of these receptors. Localization has been carried out using specific antisera raised against immunogenic peptide sequences that were subsequently applied using modern immunohistochemical techniques and confocal microscopy. The results are the first to show the presence of these receptor component proteins in human middle meningeal, middle cerebral. pial, and superficial temporal vessels, and confirm that both calcitonin gene-related peptide and adrenomedullin receptors may arise from the coassembly of RAMPs with CRLR in these vessel type,,. These novel data advance the understanding of the molecular function of the trigeminovascular system, its potential role in vascular headache disorders such as migraine. and may lead to possible Ways in which future synthetic ligands may be applied to manage these disorders.
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| 10352. |
- Olivier, Cecille, et al.
(författare)
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New strategies for the conduct of clinical trials in paediatric Pulmonary Arterial Hypertension (PAH): Outcome of a multi-stakeholder meeting with patients, academia, industry and regulators held at EMA on Monday 12th June 2017
- 2019
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 8:10, s. 1-10
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Forskningsöversikt (refereegranskat)abstract
- Aims: Drug development for paediatric pulmonary arterial hypertension (PAH) ispressingly needed. Experts from the US Food and Drug Administration, EuropeanMedicines Agency, Health Canada, key opinion leaders, academia, patients, and industry representatives held a workshop on 12th June 2017 dedicated to addressing challenges and unmet needs. This report summarises the approaches proposed during the meeting to address key issues in extrapolation, trial design, and study endpoints in pediatric drug development.Methods and Results: A pre-workshop stakeholder survey was conducted and showed that most respondents believe the pathophysiology of heritable PAH and some forms of idiopathic PAH is thought to be sufficiently similar in adult and paediatric patients, although the clinical manifestations may differ. In this situation, placebo-controlled trials might not be required to confirm clinical benefit in paediatrics. The study endpoints used to support drug approvals in adults were reviewed to determine if these existing study endpoints can be applied in paediatric PAH efficacy trials. It showed that non-invasive study endpoints, such as the time to clinical worsening, WHO functionalclass, and 6-Minute-Walk-Test could be applicable in paediatric PAH trials, although each presents some limitations in paediatrics.Conclusion: Extrapolation of efficacy from informative adult studies may be appropriate in some forms of PAH. Initial dose-finding studies and exposure-response modelling are warranted in paediatric PAH, followed by an efficacy and safety study to explore the response to treatment and exposure-response relationship. A novel, non-invasive, developmentally-appropriate, and reliable study endpoint needs to be developed.
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| 10353. |
- Olofsson, Cecilia Kjellberg, et al.
(författare)
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A national study of the outcome after treatment of critical aortic stenosis in the neonate.
- 2020
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Ingår i: Cardiology in the young. - 1467-1107. ; 30:9, s. 1321-1327
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Tidskriftsartikel (refereegranskat)abstract
- This study describes short-term and long-term outcome after treatment of critical valvular aortic stenosis in neonates in a national cohort, with surgical valvotomy as first choice intervention.All neonates in Sweden treated for critical aortic stenosis between 1994 and 2016 were included. Patient files were analysed and cross-checked against the Swedish National Population Registry as of December 2017, giving complete survival data. Diagnosis was confirmed by reviewing echo studies. Critical aortic stenosis was defined as valvular stenosis with duct-dependent systemic circulation or depressed left ventricular function. Primary outcome was all-cause mortality and secondary outcomes were reintervention and aortic valve replacement.Sixty-one patients were identified (50 boys, 11 girls). Primary treatment was surgical valvotomy in 52 neonates and balloon valvotomy in 6. Median age at initial treatment was 5 days (0-26), and median follow-up time was 10.8 years (0.14-22.6). There was no 30-day mortality but four late deaths. Freedom from reintervention was 66%, 61%, 54%, 49%, and 46% at 1, 5, 10, 15, and 20 years, respectively. Median time to reintervention was 3.4 months (4 days to 17.3 years). Valve replacement was performed in 23 patients (38%).Surgical valvotomy is a safe and reliable treatment in these critically ill neonates, with no 30-day mortality and long-term survival of 93% in this national study. At 10 years of age, reintervention was performed in 54% and at end of follow-up 38% had had an aortic valve replacement.
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| 10354. |
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| 10355. |
- Olofsson, Mona, 1952-, et al.
(författare)
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Are elderly patients with suspected HF misdiagnosed? : a primary health care center study
- 2007
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Ingår i: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 107:4, s. 226-32
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Tidskriftsartikel (refereegranskat)abstract
- Background: Few studies are published on heart failure patients in primary health care, in elderly in advanced age. Objective: The purpose of this study was to examine the accuracy of the diagnosis of heart failure in all men and women with focus on age and gender. Methods: The patients were recruited from one selected primary health care in the city of Skellefteå, Sweden. The general practitioners included all patients who had symptoms and signs indicating heart failure. The patients were then referred for an echocardiographic examination and a final cardiology consultation. Results: The general practitioners identified 121 women and 49 men with suspected heart failure of whom 39% (51 women and 16 men) were above 80 years. Women were significantly older than men (mean age 78 and 75 years, respectively, p = 0.03). The main symptom was dyspnoea (80%). Confirmed heart failure was verified in 45% of the patients and was significantly more common in men than women (p = 0.02). Of all men and women above 80 years, 75% and 22%, respectively (p = 0.01) had a verified systolic heart failure, while there were no significant gender differences in patients younger than 80. In a multivariate regression analysis taking gender, age, smoking, atrial fibrillation, hypertension, angina, myocardial infarction and diabetes into account, myocardial infarction (OR = 4.3, CL = 1.8–10.6) hypertension (OR = 3.4, CI = 1.6–6.9) atrial fibrillation (OR = 2.8, CL = 1.0–7.9) remained significantly predictive of a confirmed diagnosis of heart failure. Conclusion: This study showed the difficulty of diagnosing heart failure accurately based only on clinical symptoms, especially in women above 80 years.
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| 10356. |
- Olofsson, Mona, 1952-
(författare)
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Heart failure in elderly with focus on diagnosis and prognosis
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Patients older than 75 years with heart failure (HF) are at increased risk for mortality and hospital admissions. Echocardiography and brain natriuretic peptides (BNP, NTproBNP) are important diagnostic tools but sparsely evaluated in elderly PHC patients. Aims: Validate the clinical diagnosis of HF, investigate the types of HF and underlying cardiovascular disorders with focus on sex and age differences. Explore the sensitivity, specificity, negative and positive predictive values (NPV, PPV) of BNP and NT-proBNP in patients with systolic HF. Study the associations of HF or NTproBNP on all-cause and cardiovascular mortality. Study the prognostic value of different biomarkers and HF, on all-cause and cardiovascular hospitalizations. Methods: Patients with suspected HF were recruited from one selected PHC and registered on a prespecified record and referred for an echocardiographic examination and a final cardiologist consultation. Blood samples for natriuretic peptides were stored frozen at – 70° C. Death certificates were used to register all-cause mortality and cardiovascular mortality. To register hospitalisations, medical records were used and classification was defined according to ICD-10. Results The GPs identified 121 women and 49 men with suspected HF of whom 39% (51 women and 16 men) were above 80 years. Myocardial infarction (OR:4,3 CL: 1,8-10,6) hypertension (OR:3,4 CI:1,6-6,9) atrial fibrillation (OR:2,8 CL:1,0-7,9) predicted a confirmed diagnosis of HF. Confirmed HF was verified in 45% of the patients and was significantly more common in men than women (p=0,02). The best NPV was 88 % for NT-proBNP (200 ng/L) and 87 % for BNP (20 pg/ml). Age and male gender were independently associated with higher levels of NT-proBNP. During the 10-year follow up, 71 out of 144 patients died. In univariate Cox regression analysis, significant associations were found for overall HF (hazard ratio [HR]: 1.86; 95% confidence interval [CI]:1.15- 3.01), isolated systolic HF (HR:1.95; 95% CI:1.06-3.61), and combined (systolic and diastolic) HF (HR:3.28; 95% CI:1.74-6.14) with all-cause mortality, but not for isolated diastolic HF. In multivariable analysis, age (HR: 1.11; 95% CI: 1.06-1.17), kidney dysfunction (HR:1.91; 95% CI:1.11- 3.29), smoking (HR:3.70; 95% CI:2.02-6.77), and NTproBNP (HR:1.01; 95% CI:1.00-1.02), but not any type of HF, significantly predicted all-cause mortality. During ten years, 136 (80%) patients were hospitalised with 660 and 207 for all-cause and cardiovascular hospitalisations, respectively. Age (OR:1.1; 95% CI:1.01-1.15) and underlying heart disease (OR:3.5; 95% CI:1.00-11.89), significantly predicted all-cause hospitalisation. Overall HF (HR:1.8; 95% CI:1.06-2.94) significantly predicted time to first all-cause hospitalisations. For cardiovascular hospitalisations age (OR:1.1;95%CI:1.01-1.12), underlying heart disease (OR:3.4;95%CI:1.04-11.40) and NTproBNP ≥800 ng/L (OR:4,3;95%CI:1.5-12.50) were significant predictors. Conclusion: A confirmed diagnosis of HF was present in 45% of the patients. NPV was high, but not as high as in younger patients with HF. Patients with systolic HF had a higher mortality than patients with diastolic HF compared to patients with no HF. Patients with combined HF were at even higher risk for all-cause mortality and cardiovascular mortality. Age, kidney dysfunction, NTproBNP and smoking predicted mortality. Age and underlying heart diseases were predictors for all-cause hospitalisations and together with NTproBNP they also predicted cardiovascular hospitalisations.
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| 10357. |
- Olofsson, Mona, 1952-, et al.
(författare)
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Impact on mortality of systolic and/or diastolic heart failure in the elderly : 10 Years of follow up
- 2015
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Ingår i: Journal of Clinical Gerontology and Geriatrics. - : Elsevier. - 2210-8335 .- 2210-8343. ; 6:1, s. 20-26
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Tidskriftsartikel (refereegranskat)abstract
- Background/purpose: There is a lack of long-term follow-up studies for elderly patients with heart failure (HF) in primary health care. There is conflicting information on prognostic differences between systolic or diastolic HF in elderly patients. Our aims were, first, to study the association between overall HF or types of HF and all-cause and cardiovascular mortality, and second, to explore the impact of N-terminal prohormone of brain natriuretic peptide (NTproBNP) and comorbidities. Methods: A longitudinal, prognostic, observational primary health care study with 10 years of follow-up comparing an elderly patient population with HF (systolic and/or diastolic HF) to patients without HF was conducted. HF was diagnosed with echocardiography according to the European Society of Cardi- ology guidelines. Results: Seventy-seven of 144 patients (102 women and 42 men; mean age, 77 years) had systolic and/or diastolic HF and were compared with 67 patients without HF (Reference group). During the 10-year follow-up, 71 (49%) patients died (women, 68%; men, 32%). In univariate Cox regression analysis, sig- nificant associations were found for overall HF [hazard ratio (HR), 1.86; 95% confidence interval (CI), 1.15 e3.01], isolated systolic HF (HR, 1.95; 95% CI, 1.06e3.61), and combined (systolic and diastolic) HF (HR, 3.28; 95% CI, 1.74e6.14) with all-cause mortality, but not for isolated diastolic HF. Similar results were found for cardiovascular mortality. In multivariate analysis, age (HR, 1.11; 95% CI, 1.06e1.17), kidney dysfunction (HR, 1.91; 95% CI, 1.11e3.29), smoking (HR, 3.70; 95% CI, 2.02e6.77), and NTproBNP (HR, 1.01; 95% CI, 1.00e1.02) significantly predicted all-cause mortality, but not any type of HF. Conclusion: Patients diagnosed with systolic HF had a worse prognosis for mortality compared to the reference group, but in patients with diastolic HF the prognosis for mortality was similar with that in the reference group. NTproBNP was a valuable prognostic factor in elderly patients. Emphasis should be 1. Introduction In the elderly population (>75 years), the prevalence of heart failure (HF) is about 10%.1 The prognosis for patients with HF is poor, comparable to a diagnosis of cancer.2 Severe systolic HF has the most serious prognosis,3 but whether diastolic HF has the same ominous prognosis as systolic HF in both younger and elderly pa- tients is a matter of debate.3e5 Elderly patients, especially females, are known to more often have diastolic HF than younger patients.
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| 10358. |
- Olofsson, Mona, et al.
(författare)
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Predictors for hospitalizations in elderly patients with clinical symptoms of heart failure : a 10-year observational primary health care study
- 2016
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Ingår i: Journal of clinical gerontology & geriatrics. - : Elsevier BV. - 2210-8335. ; 7:2, s. 53-59
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Tidskriftsartikel (refereegranskat)abstract
- Background/Purpose: Heart failure (HF) is the most common cause of hospitalization at medical clinics for patients older than 65 years. Purpose: To study the prognostic value of biomarkers, comorbidities, and verified HF diagnosis for all-cause and cardiovascular hospitalizations. Methods: Between 2000 and 2003, 170 patients with HF symptoms according to their general practitioners were recruited and referred for echocardiography, biomarker measures and a final cardiology consultation. HF diagnosis was based on the general practitioner's prespecified HF record, echocardiography, and hospital records. Records from the departments of medicine and surgery were used to identify hospitalizations. This is a 10-year longitudinal observational primary healthcare center study. Results: During 10 years, 136 (80%) patients had 660 and 207 all-cause and cardiovascular hospitalizations, respectively. In multivariable logistic regression, age [ odds ratio (OR) = 1.1, 95% confidence interval (CI) = 1.01-1.15] and underlying heart disease (OR = 3.5, 95% CI = 1.00-11.89) significantly predicted all-cause hospitalization. Age (OR = 1.1, 95% CI = 1.01-1.12), underlying heart disease (OR = 3.4, 95% CI = 1.041-1.40), and N-terminal of prohormone brain natriuretic peptide >= 800 ng/L (OR = 4.3, 95% CI = 1.5-12.50) significantly predicted cardiovascular hospitalizations. In Cox regression analysis, overall HF (HR = 1.8, 95% CI = 1.06-2.94) significantly predicted time to first all-cause hospitalizations while no variable independently predicted time to first cardiovascular hospitalization. Conclusion: In patients with HF symptoms managed in primary healthcare, age, and underlying heart diseases predicted all-cause hospitalizations. N-terminal of prohormone brain natriuretic peptide added independent prognostic information for cardiovascular hospitalizations.
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| 10359. |
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| 10360. |
- Olofsson, Mona, et al.
(författare)
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Usefulness of natriuretic peptides in primary health care : an exploratory study in elderly patients
- 2010
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Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 28:1, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To explore the negative predictive value (NPV), positive predictive value (PPV), sensitivity, and specificity of natriuretic peptides, cut-off levels, and the impact of gender and age in elderly patients with systolic heart failure (HF). Design. Cross-sectional exploratory study. Setting. One primary healthcare centre. Patients. A total of 109 patients with symptoms of HF were referred for echocardiographic examination with a cardiovascular consultation. Systolic HF was diagnosed (ESC guidelines) in 48 patients (46% men, 54% women, mean age 79 years) while 61 patients (21% men, 79% women, mean age 76 years) had no HF. Main outcome measures. NPV, PPV, sensitivity, specificity, and cut-off levels. Results. Including all 109 patients, NPV was 88% for NT-proBNP (200 ng/L) and 87% for BNP (20 pg/ml). PPV was 81% for NT-proBNP (500 ng/L) and 68% for BNP (50 pg/ml). Sensitivity was 96% for NT-proBNP (100 ng/L) and 96% for BNP (10-20 pg/ml). Specificity was 87% for NT-proBNP (500 ng/L) and 71% for BNP (50 pg/ml). Nt-proBNP (beta = 0.035; p < 0.001) and BNP (beta = 0.030; p < 0.001) were associated with age, but not with gender. In a multivariate analysis age (beta = 0.036; p < 0.001) and male gender (beta = 0.270; p = 0.014) were associated with NT-proBNP, but only age for BNP (beta = 0.030; p < 0.001). Conclusion. Natriuretic peptides in an elderly population showed high NPVs, but not as high as in younger patients with HF in other studies. Age and male gender were associated with higher levels of NT-proBNP while only age was related to elevated BNP levels.
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