| 1. |
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| 2. |
- Carlsson, Per, 1951-, et al.
(författare)
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National Model for Transparent Vertical Prioritisation in Swedish Health Care
- 2007
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The proposed national model described in this report has been developed by a working group comprised of staff from the National Board of Health and Welfare, the National Centre for Priority Setting in Health Care, and other organisations involved in vertical prioritisation – including the Östergötland County Council, Stockholm County Council, Västra Götaland, the Health Services Region of Southern Sweden, the Swedish Society of Medicine, the Swedish Society of Nursing, and the Swedish Association of Health Professionals. Throughout the process of designing the model, the Swedish Federation of Occupational Therapists and the Swedish Association of Registered Physiotherapists were regularly informed and given opportunities to review and comment on the proposal. Furthermore, the report was reviewed and discussed at a meeting with invited representatives from the other county councils, the Pharmaceutical Benefits Board, and several professional interest groups. Viewpoints were also obtained at a seminar arranged by PrioNet, a network of individuals interested in prioritisation.Potentially, the working model described in Chapter 4 could be used in any context where vertical prioritisation takes place, e.g. activities arranged by the state, county councils, municipalities, hospital departments, and professional groups.This report is designed to be a useful tool for those working on development projects in priority setting. We believe that the contents must be adapted, with the help of relevant examples and some simplifications; to fit the specific needs of different projects or groups. The text must also be adapted to a target group’s knowledge and previous experience in dealing with transparent priority setting. It must be the responsibility of each provider and other affected organisation to adapt the material to the given situation and project. The National Centre for Priority Setting in Health Care, the National Board of Health and Welfare, and others who have participated actively in this effort can be helpful to various target groups in adapting this report.When and how to engage in practically implementing vertical prioritisation are questions that need to be answered at the local level. Primarily, it is the duty of the local authorities/providers to take responsibility for implementation. Professional organisations also play an important role. Public agencies, universities, and knowledge centres should be sources of support for the local authorities/providers.The Riksdag’s resolution on prioritisation served as the foundation for developing the model.Where there are areas of uncertainty in how to translate these guidelines in practice, or where practical implementation might conflict with the principles, we have pointed this out.Our conclusions and proposals are the following:When facing a choice – regardless of whether it involves allocating new resources for different purposes, or to implement cutbacks – it can be advantageous to rank the possible choices in order of priority. In our model, only the relevant options can be ranked by priority. The consequences of this ranking are not obvious at the outset, but can serve as a basis either to allocate more resources or ration by some means.In vertical prioritisation, it is advantageous to organise the prioritization process starting from a general categorisation of health problems/disease groups. As a rule, these categories cover many organisational units/clinical departments, specialties, or professional groups, thus providing a more multidimensional view of the problem. Furthermore, this allows the process to start from a patient/population perspective, which appears to be more goal-oriented than an organisational/staff perspective.That which is ranked, i.e. one of the choices, we refer to as a prioritization object. We suggest that prioritisation objects consist of different combinations of health conditions and interventions.1 When deciding on the appropriate level of detail, the decision must be based on the context in which prioritisation is carried out. A starting point would be to focus on typical cases, large-volumes services, and controversial care.All forms of vertical prioritisation should be based on the ethical principles that the Riksdag decided should apply in prioritising health services. However, these ethical principles must be made known, clarified, and perhaps complemented before they can be applied to practical priority setting. Furthermore, we believe that the Riksdag’s four so-called priority groups should not be part of the model.The human dignity principle, i.e. that all people should have equal value and equal rights to care irrespective of their personal characteristics and function in society, is the undisputed cornerstone in priority setting. When personal characteristics such as age, gender, lifestyle, or function of a group are expressions of the presence of special needs, so that benefits of the interventions are different, these personal characteristics could be addressed in a priority at the group level. Further discussion is needed regarding the question of how external effects (i.e. the effects of an intervention on families and groups other than the individual directly affected by the intervention) should be valued in priority setting.The concept of need in health care includes both the severity level of the condition and the expected benefits of intervention. As a patient, one needs only those interventions that can be expected to yield benefits. Based on this definition of need, a person does not need an intervention that does not improve health and quality of life, i.e. an intervention with no benefit. In such cases, health services have a responsibility to refer people who seek care for some type of problem, to other appropriate services.The Riksdag’s guidelines regarding the cost-effectiveness principle (applied to individual patients) are too limited to provide guidance for vertical prioritisation at the group level. From the outset, the Government’s bill (Priority Setting in Health Care) highlighted the importance of differentiating a cost-effectiveness principle that applied to choices among various interventions for the individual patient (where the principle can be applied as the Commission of Inquiry proposed) and the aim of health services to achieve high cost-effectiveness in health care generally. Here we also refer to the Riksdag’s directive to the Pharmaceutical Benefits Board. In its decisions on subsidising (prioritising) a drug, the Board should determine, e.g. whether the drug is cost effective from a societal perspective, which requires comparing the patient benefits of the drug to its cost. In such decisions, the cost effectiveness should be considered along with the needs and solidarity principle and the human dignity principle.The proposed working model essentially concurs with the working model used by the National Board of Health and Welfare in developing national guidelines. In describing a national working model, it is not possible to include every aspect that might be considered. Hence, one must start from the model and decide which other relevant aspects should be included. For instance, the International Classification on Functioning, Disability, and Health (ICF) can be used as guidance to describe the severity of health conditions.Due to the wealth of variety in outcome measures for different activities, and the limited experience in working with explicit threshold values, we believe would be premature to recommend standardised categories, e.g. risk levels. However, it is important that those working with prioritization describe their reasoning. Primarily, the categories applied by the Swedish Council on Technology Assessment in Health Care (SBU) to grade the scientific evidence of an intervention’s effects should be used. Local prioritisation projects with limited resources at their disposal should describe (text) their appraisal of the scientific evidence and reference the scientific sources used. The strength of evidence should be expressed in numbers only when supporting a conclusion of a systematic review by SBU, or other literature reviews of good quality.Prioritisation projects having access to health economic evaluation should, until further notice, adhere to the approach used by the National Board of Health and Welfare and present cost-effectiveness on a scale from low to very high cost per life-year gained or cost per quality-adjusted life-year. Economic evidence should be presented according to the principles applied by the National Board of Health and Welfare. In local projects with limited resources, or problems in consistently acquiring information on cost effectiveness, we recommend that the authors at least discuss cost effectiveness in cases where the priority ranking would be decisively affected when costs are weighed in.A 10-level ranking list should be used. The ranking list should be complemented by a “don’t do” list for methods that should not be used at all, or not used routinely, and a research and development (R&D) list for methods where the evidence still insufficient to motivate their use in standard practice. In the absence of an objective quantitative/mathematical method, a qualitative method should be used in the appraisal. Here too, we believe that it is not yet possible to establish standard criteria to determine within which ranking level a prioritisation object should fall.Results should be presented as a ranking list. The parameters used as a basis for prioritisation should also be presented in a uniform manner in ranking lists that are shared with other parties. For pedagogic reasons, details concerning language and format need to be adapted to the respective target groups.Thresholds for what constitutes an acceptable coverage of need (care quality, volume, and percentage of the patient group with access to services) a
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| 3. |
- Haahr, Thor, et al.
(författare)
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Vaginal dysbiosis in pregnancy associates with risk of emergency caesarean section: a prospective cohort study
- 2022
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Ingår i: Clinical Microbiology and Infection. - Oxford, United Kingdom : Elsevier. - 1198-743X .- 1469-0691. ; 28:4, s. 588-595
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate changes in vaginal microbiota during pregnancy, and the association between vaginal dysbiosis and reproductive outcomes.Methods: A total of 730 (week 24) and 666 (week 36) vaginal samples from 738 unselected pregnant women were studied by microscopy (Nugent score) and characterized by 16S rRNA gene sequencing. A novel continuous vaginal dysbiosis score was developed based on these methods using a supervised partial least squares model.Results: Among women with bacterial vaginosis in week 24 (n = 53), 47% (n = 25) also had bacterial vaginosis in week 36. In contrast, among women without bacterial vaginosis in week 24, only 3% (n = 18) developed bacterial vaginosis in week 36. Vaginal samples dominated by Lactobacillus crispatus (OR 0.35, 95% CI 0.20–0.60) and Lactobacillus iners (OR 0.40, 95% CI 0.23–0.68) in week 24 were significantly more stable by week 36 when compared with other vaginal community state types. Vaginal dysbiosis score at week 24 was associated with a significant increased risk of emergency, but not elective, caesarean section (OR 1.37, 955 CI 1.15–1.64, p < 0.001), suggesting a 37% increased risk per standard deviation increase in vaginal dysbiosis score.Conclusions: Changes in vaginal microbiota from week 24 to week 36 of pregnancy correlated with bacterial vaginosis status and vaginal community state type. A novel vaginal dysbiosis score was associated with a significantly increased risk of emergency, but not elective, caesarean section. This was not found for bacterial vaginosis or any vaginal community state type and could point to the importance of investigating vaginal dysbiosis as a nuanced continuum instead of crude clusters.
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| 4. |
- Kofod Vinding, Rebecca, et al.
(författare)
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Fish Oil Supplementation in Pregnancy Increases Gestational Age, Size for Gestational Age, and Birth Weight in Infants: A Randomized Controlled Trial
- 2019
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 149:4, s. 628-634
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Randomized trials have reported that supplementation with n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in pregnancy can prolong pregnancy and thereby increase birth weight. OBJECTIVE: We aimed to examine the relations of n-3 LCPUFA supplementation in pregnancy with duration of pregnancy, birth weight, and size for gestational age (GA). METHODS: This was a double-blind randomized controlled trial conducted in 736 pregnant women and their offspring, from the Copenhagen Prospective Studies on Asthma in Childhood2010cohort. They were recruited between weeks 22 and 26 in pregnancyand randomly assigned to either of 2.4 g n-3 LCPUFA or control (olive oil) daily until 1 wk after birth. Exclusion criteria were endocrine, cardiovascular, or nephrologic disorders and vitamin D supplementation intake >600 IU/d. In this study we analyzed secondary outcomes, and further excluded twin pregnancies and extrauterine death. The primary outcome for the trial was persistent wheeze or asthma. RESULTS: The random assignment ran between 2008 and 2010. Six hundred and ninety-nine mother-infant pairs were included in the analysis. n-3 LCPUFA compared with control was associated with a 2-d prolongation of pregnancy [median (IQR): 282 (275-288) d compared with 280 (273-286) d, P = 0.02], a 97-g higher birth weight (mean ± SD: 3601 ± 534 g compared with 3504 ± 528 g, P = 0.02), and an increased size for GA according to the Norwegian population-based growth curves-Skjærven (mean ± SD: 49.9 ± 28.3 percentiles compared with 44.5 ± 27.6 percentiles, P = 0.01). CONCLUSION: Supplementing pregnant women with n-3 LCPUFAs during the third trimester is associated with prolonged gestation and increased size for GA, leading to a higher birth weight in this randomized controlled trial. This trial was registered at clinicaltrials.gov as NCT00798226.
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| 5. |
- Liu, Xueping, et al.
(författare)
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Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P=3.96×10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.
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| 6. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 7. |
- van der Valk, Ralf J P, et al.
(författare)
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A novel common variant in DCST2 is associated with length in early life and height in adulthood.
- 2015
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
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Tidskriftsartikel (refereegranskat)abstract
- Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
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| 8. |
- Vogelezang, Suzanne, et al.
(författare)
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Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
- 2020
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10
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Tidskriftsartikel (refereegranskat)abstract
- The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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| 9. |
- Abel, Marianne Hope, et al.
(författare)
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Insufficient maternal iodine intake is associated with subfecundity, reduced foetal growth, and adverse pregnancy outcomes in the Norwegian Mother, Father and Child Cohort Study.
- 2020
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Ingår i: BMC medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Severe iodine deficiency impacts fertility and reproductive outcomes. The potential effects of mild-to-moderate iodine deficiency are not well known. The aim of this study was to examine whether iodine intake was associated with subfecundity (i.e. >12months trying to get pregnant), foetal growth, and adverse pregnancy outcomes in a mild-to-moderately iodine-deficient population.We used the Norwegian Mother, Father and Child Cohort Study (MoBa) and included 78,318 pregnancies with data on iodine intake and pregnancy outcomes. Iodine intake was calculated using an extensive food frequency questionnaire in mid-pregnancy. In addition, urinary iodine concentration was available in a subsample of 2795 pregnancies. Associations were modelled continuously by multivariable regression controlling for a range of confounding factors.The median iodine intake from food was 121μg/day and the median urinary iodine was 69μg/L, confirming mild-to-moderate iodine deficiency. In non-users of iodine supplements (n=49,187), low iodine intake (<100-150μg/day) was associated with increased risk of preeclampsia (aOR=1.14 (95% CI 1.08, 1.22) at 75 vs. 100μg/day, p overall <0.001), preterm delivery before gestational week 37 (aOR=1.10 (1.04, 1.16) at 75 vs. 100μg/day, p overall=0.003), and reduced foetal growth (-0.08 SD (-0.10, -0.06) difference in birth weight z-score at 75 vs. 150μg/day, p overall <0.001), but not with early preterm delivery or intrauterine death. In planned pregnancies (n=56,416), having an iodine intake lower than ~100μg/day was associated with increased prevalence of subfecundity (aOR=1.05 (1.01, 1.09) at 75μg/day vs. 100μg/day, p overall=0.005). Long-term iodine supplement use (initiated before pregnancy) was associated with increased foetal growth (+0.05 SD (0.03, 0.07) on birth weight z-score, p<0.001) and reduced risk of preeclampsia (aOR 0.85 (0.74, 0.98), p=0.022), but not with the other adverse pregnancy outcomes. Urinary iodine concentration was not associated with any of the dichotomous outcomes, but positively associated with foetal growth (n=2795, p overall=0.017).This study shows that a low iodine intake was associated with restricted foetal growth and a higher prevalence of preeclampsia in these mild-to-moderately iodine-deficient women. Results also indicated increased risk of subfecundity and preterm delivery. Initiating iodine supplement use in pregnancy may be too late.
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| 10. |
- Aberšek, Nina, et al.
(författare)
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Calprotectin levels in amniotic fluid in relation to intra-amniotic inflammation and infection in women with preterm labor with intact membranes: A retrospective cohort study
- 2022
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Ingår i: European Journal of Obstetrics & Gynecology and Reproductive Biology. - : Elsevier BV. - 1872-7654 .- 0301-2115. ; 272, s. 24-29
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the concentrations of calprotectin in amniotic fluid with respect to intra-amniotic inflammation and infection and to assess the presence or absence of bacteria in the amnio-chorionic niche with respect to presence or absence of intra-amniotic inflammation. Study design: Seventy-nine women with singleton pregnancies and preterm labor with intact membranes (PTL) were included in the study. Amniotic fluid was collected at the time of admission by amniocentesis and calprotectin levels were analyzed from frozen/thawed samples using ELISA. Interleukin (IL)-6 concentration was measured by point-of-care test. Samples from amniotic fluid and the amnio-chorionic niche (space between amniotic and chorionic membranes) were microbiologically analyzed. Microbial invasion of the amniotic cavity (MIAC) was diagnosed based on a positive PCR result for Ureaplasma species, Mycoplasma hominis, 16S rRNA or positive culture. Intra-amniotic inflammation (IAI) was defined as amniotic fluid point-of-care IL-6 concentration ≥ 745 pg/mL. The cohort of included women was divided into 4 subgroups based on the presence or absence of IAI/MIAC; i) intra-amniotic infection, ii) sterile IAI, iii) intra-amniotic colonization and iv) neither MIAC nor IAI. Results: Women with intra-amniotic infection had a significantly higher intra-amniotic calprotectin concentration (median; 101.6 µg/mL) compared with women with sterile IAI (median; 9.2 µg/mL), women with intra-amniotic colonization (median; 2.6 µg/mL) and women with neither MIAC nor IAI (median 4.6 µg/mL) (p = 0.001). Moreover, significantly higher amniotic fluid calprotectin concentration was seen in women who delivered within 7 days (p = 0.003). A significant negative correlation was found between amniotic fluid calprotectin and gestational age at delivery (rho = 0.32, p = 0.003). Relatively more bacteria in the amnio-chorionic niche were found in the sterile IAI group compared with the other groups. Conclusions: Calprotectin concentrations in amniotic fluid were significantly higher in the intra-amniotic infection group compared with the other groups. Moreover, the bacterial presence in the amnio-chorionic niche was higher in IAI group.
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