| 1. |
- Artigas Soler, María, et al.
(författare)
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Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
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| 2. |
- Loth, Daan W, et al.
(författare)
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Genome-wide association analysis identifies six new loci associated with forced vital capacity
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
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Tidskriftsartikel (refereegranskat)abstract
- Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
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| 3. |
- Sakornsakolpat, Phuwanat, et al.
(författare)
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Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
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| 4. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 5. |
- Havnes, Kjerstin, et al.
(författare)
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Time distribution for pharmacists conducting a randomized controlled trial - An observational time and motion study
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionAn expected future increase in older adults will demand changes in health care delivery, making development, implementation and evaluation of new health care models essential. The rationale for political decision-making concerning the implementation and application of interventions in health care should include cost estimations, specifically those involving clinical interventions. To provide such data knowledge of time spent on the intervention is imperative. Time and motion methodology is suitable to quantify health care personnel’s time distribution.AimTo investigate the time distribution for pharmacists conducting a randomized controlled trial (RCT) implementing a clinical intervention.Materials and methodsThe setting was an RCT with a 5-step pharmacist-intervention in collaboration with the interdisciplinary team in a geriatric ward. Two pharmacists were involved in the trial during the observation period. Pharmacist activities, classified as RCT-tasks (intervention or administrative), non-RCT tasks and social/breaks, were recorded applying the Work Observation Method By Activity Timing methodology, enabling recording of predefined work tasks as well as interruptions and multitasking. One observer collected data over eight weeks.ResultsIn total, 109.1 hours were observed resulting in 110.2 hours total task time, including multitasking. RCT tasks comprised 85.4% of the total observed time, and nearly 60% of the RCT time was spent on intervention tasks. Medication reviews was the most time consuming task, accounting for 32% of the observed time. The clinical pharmacists spent 14% of the intervention time communicating verbally, mainly with patients and healthcare professionals.ConclusionDuring the RCT, the clinical pharmacists spent about half their time performing the actual intervention. Consequently, costs for providing such a clinical pharmacist service should reflect actual time spent; otherwise, we may risk overestimating theoretical costs.
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| 6. |
- Ulaszewska, Marynka M., et al.
(författare)
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Nutrimetabolomics: An Integrative Action for Metabolomic Analyses in Human Nutritional Studies
- 2019
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Ingår i: Molecular Nutrition and Food Research. - : Wiley. - 1613-4125 .- 1613-4133. ; 63:1
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Forskningsöversikt (refereegranskat)abstract
- The life sciences are currently being transformed by an unprecedented wave of developments in molecular analysis, which include important advances in instrumental analysis as well as biocomputing. In light of the central role played by metabolism in nutrition, metabolomics is rapidly being established as a key analytical tool in human nutritional studies. Consequently, an increasing number of nutritionists integrate metabolomics into their study designs. Within this dynamic landscape, the potential of nutritional metabolomics (nutrimetabolomics) to be translated into a science, which can impact on health policies, still needs to be realized. A key element to reach this goal is the ability of the research community to join, to collectively make the best use of the potential offered by nutritional metabolomics. This article, therefore, provides a methodological description of nutritional metabolomics that reflects on the state-of-the-art techniques used in the laboratories of the Food Biomarker Alliance (funded by the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL)) as well as points of reflections to harmonize this field. It is not intended to be exhaustive but rather to present a pragmatic guidance on metabolomic methodologies, providing readers with useful “tips and tricks” along the analytical workflow.
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| 7. |
- Zahl-Holmstad, Birgitte, et al.
(författare)
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Completeness of medication information in admission notes from emergency departments
- 2023
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Ingår i: BMC Health Services Research. - : BioMed Central (BMC). - 1472-6963. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMedication lists prepared in the emergency department (ED) form the basis for diagnosing and treating patients during hospitalization. Since incomplete medication information may lead to patient harm, it is crucial to obtain a correct and complete medication list at hospital admission. In this cross-sectional retrospective study we wanted to explore medication information completeness in admission notes from Norwegian EDs and investigate which factors were associated with level of completeness.MethodsMedication information was assessed for completeness by applying five evaluation criteria; generic name, formulation, dose, frequency, and indication for use. A medication completeness score in percent was calculated per medication, per admission note and per criterion. Quantile regression analysis was applied to investigate which variables were associated with medication information completeness.ResultsAdmission notes for patients admitted between October 2018 and September 2019 and using at least one medication were included. A total of 1,080 admission notes, containing 8,604 medication orders, were assessed. The individual medications had a mean medication completeness score of 88.1% (SD 16.4), while admission notes had a mean medication completeness score of 86.3% (SD 16.2). Over 90% of all individual medications had information about generic name, formulation, dose and frequency stated, while indication for use was only present in 60%. The use of an electronic tool to prepare medication information had a significantly strong positive association with completeness. Hospital visit within the last 30 days, the patient's living situation, number of medications in use, and which hospital the patient was admitted to, were also associated with information completeness.ConclusionsMedication information completeness in admission notes was high, but potential for improvement regarding documentation of indication for use was identified. Applying an electronic tool when preparing admission notes in EDs seems crucial to safeguard completeness of medication information.
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| 8. |
- Dastani, Zari, et al.
(författare)
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Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals
- 2012
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002607-
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Tidskriftsartikel (refereegranskat)abstract
- Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P=4.5 x 10(-8)-1.2 x 10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3 x 10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p=4.3 x 10(-3), n = 22,044), increased triglycerides (p=2.6 x 10(-14), n = 93,440), increased waist-to-hip ratio (p=1.8 x 10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p=4.4 x 10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p=4.5x10(-13), n = 96,748) and decreased BMI (p= 1.4 x 10(-14), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
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| 9. |
- Robinson, Eirin Guldsten, et al.
(författare)
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A Trial-Based Cost-Utility Analysis of a Medication Optimization Intervention Versus Standard Care in Older Adults.
- 2023
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Ingår i: Drugs & aging. - 1179-1969. ; 40:12, s. 1143-1155
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Tidskriftsartikel (refereegranskat)abstract
- Older adults are at greater risk of medication-related harm than younger adults. The Integrated Medication Management model is an interdisciplinary method aiming to optimize medication therapy and improve patient outcomes.We aimed to investigate the cost effectiveness of a medication optimization intervention compared to standard care in acutely hospitalized older adults.A cost-utility analysis including 285 adults aged ≥70 years was carried out alongside the IMMENSE study. Quality-adjusted lifeyears (QALYs) were derived using the EuroQol 5-Dimension 3-Level Health State Questionnaire (EQ-5D-3L). Patient-level data for healthcare use and costs were obtained from administrative registers, taking a healthcare perspective. The incremental cost-effectiveness ratio was estimated for a 12-month follow-up and compared to a societal willingness-to-pay range of €/QALY 27,067-81,200 (NOK 275,000-825,000). Because of a capacity issue in a primary care resulting in extended hospital stays, a subgroup analysis was carried out for non-long and long stayers with hospitalizations <14 days or ≥14 days.Mean QALYs were 0.023 [95% confidence interval [CI] 0.022-0.025] higher and mean healthcare costs were €4429 [95% CI -1101 to 11,926] higher for the intervention group in a full population analysis. This produced an incremental cost-effectiveness ratio of €192,565/QALY. For the subgroup analysis, mean QALYs were 0.067 [95% CI 0.066-0.070, n = 222] and -0.101 [95% CI -0.035 to 0.048, n = 63] for the intervention group in the non-long stayers and long stayers, respectively. Corresponding mean costs were €-824 [95% CI -3869 to 2066] and €1992 [95% CI -17,964 to 18,811], respectively. The intervention dominated standard care for the non-long stayers with a probability of cost effectiveness of 93.1-99.2% for the whole willingness-to-pay range and 67.8% at a zero willingness to pay. Hospitalizations were the main cost driver, and readmissions contributed the most to the cost difference between the groups.According to societal willingness-to-pay thresholds, the medication optimization intervention was not cost effective compared to standard care for the full population. The intervention dominated standard care for the non-long stayers, with a high probability of cost effectiveness.The IMMENSE trial was registered in ClinicalTrials.gov on 28 June, 2016 before enrolment started (NCT02816086).
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| 10. |
- Robinson, Eirin Guldsten, et al.
(författare)
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Health-related quality of life among older adults following acute hospitalization: longitudinal analysis of a randomized controlled trial
- 2024
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Ingår i: QUALITY OF LIFE RESEARCH. - 0962-9343 .- 1573-2649. ; 33, s. 2219-2233
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To describe the longitudinal change of health-related quality of life (HRQoL) over 12 months from acute hospitalization in older adults >= 70 years (IMMENSE study), and associated factors, to investigate how a medication optimization intervention influenced this change. Methods The EQ-5D-3L was used at discharge and 1, 6 and 12 months after discharge during a randomized controlled trial including 285 participants. Multilevel logistic (EQ-5D-3L dimensions) and mixed model regression (EQ-5D-3L index scores, EQ-VAS) were used to explore the longitudinal change with/without the intervention, and associations with medications, comorbidities, and socioeconomic variables. Subgroup analyses were performed for non-long and long stayers with hospitalizations < or >= 14 days. Results EQ-5D-3L index scores significantly declined after 12 months (beta -0.06 [95% confidence interval (CI:) -0.10--0.02], p = 0.003). Non-long stayers showed significant improvement 1 month from discharge (beta 0.05 [0.00-0.09], p = 0.040). The number of medications and receiving home-care services were the main factors associated with reduced HRQoL. Being home-dwelling was the main factor associated with higher HRQoL. Non-long stayers of the intervention group reported significantly higher EQ-VAS than the control group (beta 4.02 [0.11-7.93], p = 0.044). Conclusion We observed no significant difference in the longitudinal change in HRQoL between the two IMMENSE study groups over 12 months after hospitalization. However, the non-long stayer subgroup analysis indicates that the intervention may have had a long-term effect on HRQoL in some of intervention patients. The number of medications and the ability to live and care for oneself should be taken into consideration when planning future patient care and health-care services.
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