| 1. |
- Goossens, Maria E., et al.
(författare)
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International pooled study on diet and bladder cancer : the bladder cancer, epidemiology and nutritional determinants (BLEND) study: design and baseline characteristics
- 2016
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Ingår i: Archives of Public Health. - : BMC. - 0778-7367 .- 2049-3258. ; 74
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 2012, more than 400,000 urinary bladder cancer cases occurred worldwide, making it the 7th most common type of cancer. Although many previous studies focused on the relationship between diet and bladder cancer, the evidence related to specific food items or nutrients that could be involved in the development of bladder cancer remains inconclusive. Dietary components can either be, or be activated into, potential carcinogens through metabolism, or act to prevent carcinogen damage. Methods/design: The BLadder cancer, Epidemiology and Nutritional Determinants (BLEND) study was set up with the purpose of collecting individual patient data from observational studies on diet and bladder cancer. In total, data from 11,261 bladder cancer cases and 675,532 non-cases from 18 case-control and 6 cohort studies from all over the world were included with the aim to investigate the association between individual food items, nutrients and dietary patterns and risk of developing bladder cancer. Discussion: The substantial number of cases included in this study will enable us to provide evidence with large statistical power, for dietary recommendations on the prevention of bladder cancer.
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| 2. |
- Johansson, Emily White, 1976-
(författare)
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Beyond “test and treat” : Malaria diagnosis for improved pediatric fever management in sub-Saharan Africa
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis examined malaria test use, adherence and integration into clinical practice for improved pediatric fever management in sub-Saharan African countries and explored Access, Facility Readiness and Clinical Practice bottlenecks to achieve this program goal.Study I examined diagnostic testing rates and its determinants for pediatric fevers across 13 countries in 2009-2012 including Access bottlenecks. Study II evaluated the effect of testing on treatment decisions at the population level in 12 countries in 2010-2012 and explored reasons for varying country results across Access, Facility Readiness and Clinical Practice bottlenecks. Study III explored Facility Readiness and Clinical Practice bottlenecks for using malaria diagnosis for improved pediatric fever management in Mbarara District Uganda. Study IV examined integrated pediatric fever management using RDT and IMCI in Malawi health facilities in 2013-2014 including Facility Readiness and Clinical Practice bottlenecks.Malaria testing of pediatric fevers was low (17%) and inequitable at the outset of new guidelines with febrile children in least poor household more often tested than in poorest (OR: 1.63, 95% CI: 1.39-1.91) (Study I). Significant variability was found in the effect of testing on ACT use across countries (e.g. Uganda OR: 0.84, 95% CI: 0.66-1.06; Mozambique OR: 3.54, 95% CI: 2.33-5.39). Four main themes explained varying results: available diagnostics and medicines; quality of care; care-seeking behavior; and malaria epidemiology (Study II). In Mbarara District Uganda malaria over-treatment for RDT-negative results reportedly occurred and was driven by RDT perceptions, system constraints and provider-client interactions (Study III). In Malawi health facilities, there was common compliance to malaria treatment guidelines in sick child consultations. 72% were tested or referred for malaria diagnosis and 85% with RDT-confirmed malaria were prescribed first-line anti-malarials. Yet integrated pediatric fever management was sub-optimal in terms of other assessments completed and antibiotic targeting. 28% with IMCI-pneumonia were not prescribed any antibiotic and 59% ‘without antibiotic need’ were prescribed any antibiotic. Few eligible clients had respiratory rates counted to identify antibiotic need for IMCI-pneumonia (18%). RDT-negative children had 16.8 (95% CI: 8.6-32.7) times higher antibiotic over-treatment odds compared to positive cases and this effect was conditioned by cough or difficult breathing complaints (Study IV).Thesis findings highlight Access, Facility Readiness and Clinical Practice bottlenecks that need to be addressed to use malaria diagnosis for improved pediatric fever management. Programs must move beyond malaria-focused ‘test and treat’ strategies towards ‘IMCI with testing’ in order to conceptualize RDT as one part of the established algorithm for managing sick children in an integrated manner. RDT should also be viewed as an important entry point for contributing to ongoing health system strengthening efforts.
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| 3. |
- Johansson, Emily White
(författare)
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Beyond 'test and treat' - malaria diagnosis for improved pediatric fever management in sub-Saharan Africa
- 2016
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Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 9, s. 1-14
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Forskningsöversikt (refereegranskat)abstract
- Background: Malaria rapid diagnostic tests (RDTs) have great potential to improve quality care and rational drug use in malaria-endemic settings although studies have shown common RDT non-compliance. Yet, evidence has largely been derived from limited hospital settings in few countries. This article reviews a PhD thesis that analyzed national surveys from multiple sub-Saharan African countries to generate large-scale evidence of malaria diagnosis practices and its determinants across different contexts. Design: A mixed-methods approach was used across four studies that included quantitative analysis of national household and facility surveys conducted in multiple sub-Saharan African countries at the outset of new guidelines (Demographic and Health Surveys and Service Provision Assessments). Qualitative methods were used to explore reasons for quantitative findings in select settings. Results: There was low (17%) and inequitable test uptake across 13 countries in 2009-2011/ 12, with greater testing at hospitals than at peripheral clinics (odds ratio [OR]: 0.62, 95% confidence interval [CI]: 0.56-0.69) or community health workers (OR: 0.31, 95% CI: 0.23-0.43) (Study I). Significant variation was found in the effect of diagnosis on antimalarial use at the population level across countries (Uganda OR: 0.84, 95% CI: 0.66-1.06; Mozambique OR: 3.54, 95% CI: 2.33-5.39) (Study II). A Malawi national facility census indicated common compliance to malaria treatment guidelines (85% clients with RDT-confirmed malaria prescribed first-line treatment), although other fever assessments were not often conducted and there was poor antibiotic targeting (59% clients inappropriately prescribed antibiotics). RDT-negative patients had 16.8 (95% CI: 8.6- 32.7) times higher odds of antibiotic overtreatment than RDT-positive patients conditioned by cough or difficult breathing complaints (Study III). In Mbarara (Uganda), health workers reportedly prescribed antimalarials to RDT-negative patients if no other fever cause was identified and non-compliance seemed further driven by RDT perceptions, system constraints, and client interactions (Study IV). Conclusions: A shift from malaria-focused test and treat strategies toward IMCI with testing is needed to improve quality care and rational use of both antimalarial and antibiotic medicines. Strengthened health systems are also needed to support quality clinical care, including adherence to malaria test results, and RDT deployment should be viewed as a unique opportunity to contribute to these important efforts.
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| 4. |
- Johansson, Emily White, et al.
(författare)
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Integrated paediatric fever management and antibiotic over-treatment in Malawi health facilities: data mining a national facility census
- 2016
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Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are growing concerns about irrational antibiotic prescription practices in the era of test-based malaria case management. This study assessed integrated paediatric fever management using malaria rapid diagnostic tests (RDT) and Integrated Management of Childhood Illness (IMCI) guidelines, including the relationship between RDT-negative results and antibiotic over-treatment in Malawi health facilities in 2013-2014. Methods: A Malawi national facility census included 1981 observed sick children aged 2-59 months with fever complaints. Weighted frequencies were tabulated for other complaints, assessments and prescriptions for RDT-confirmed malaria, IMCI-classified non-severe pneumonia, and clinical diarrhoea. Classification trees using model-based recursive partitioning estimated the association between RDT results and antibiotic over-treatment and learned the influence of 38 other input variables at patient-, provider- and facility-levels. Results: Among 1981 clients, 72 % were tested or referred for malaria diagnosis and 85 % with RDT-confirmed malaria were prescribed first-line anti-malarials. Twenty-eight percent with IMCI-pneumonia were not prescribed antibiotics (under-treatment) and 59 % 'without antibiotic need' were prescribed antibiotics (over-treatment). Few clients had respiratory rates counted to identify antibiotic need for IMCI-pneumonia (18 %). RDT-negative children had 16.8 (95 % CI 8.6-32.7) times higher antibiotic over-treatment odds compared to RDT-positive cases conditioned by cough or difficult breathing complaints. Conclusions: Integrated paediatric fever management was sub-optimal for completed assessments and antibiotic targeting despite common compliance to malaria treatment guidelines. RDT-negative results were strongly associated with antibiotic over-treatment conditioned by cough or difficult breathing complaints. A shift from malaria-focused 'test and treat' strategies toward 'IMCI with testing' is needed to improve quality fever care and rational use of both anti-malarials and antibiotics in line with recent global commitments to combat resistance.
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| 5. |
- Johansson, Emily White, 1976-, et al.
(författare)
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"It could be viral, but you don't know. You have not diagnosed it" : Health worker challenges in managing non-malaria pediatric fevers in the low transmission area of Mbarara District, Uganda
- 2016
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Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 2012, Uganda initiated nationwide deployment of malaria rapid diagnostic tests (RDT) as recommended by national guidelines. Yet growing concerns about RDT non-compliance in various settings have spurred calls to deploy RDT as part of enhanced support packages. An understanding of how health workers currently manage non-malaria fevers, particularly for children, and challenges faced in this work should also inform efforts. Methods: A qualitative study was conducted in the low transmission area of Mbarara District (Uganda). In-depth interviews with 20 health workers at lower level clinics focused on RDT perceptions, strategies to differentiate non-malaria pediatric fevers, influences on clinical decisions, desires for additional diagnostics, and any challenges in this work. Seven focus group discussions were conducted with caregivers of children less than five years in facility catchment areas to elucidate their RDT perceptions, understandings of non-malaria pediatric fevers and treatment preferences. Data were extracted into meaning units to inform codes and themes in order to describe response patterns using a content analysis approach. Findings: Differential diagnosis strategies included studying fever patterns, taking histories, assessing symptoms and analyzing other factors such as child’s age or home environment. If no alternative cause was found, malaria treatment was reportedly often prescribed despite a negative result. Other reasons for malaria over-treatment stemmed from RDT perceptions, system constraints and provider-client interactions. RDT perceptions included mistrust driven largely by expectations of false negative results due to low parasite/antigen loads, previous anti-malarial treatment or test detection of only one species. System constraints included poor referral systems, working alone without opportunity to confer on difficult cases, and lacking skills and/or tools for differential diagnosis. Provider-client interactions included reported caregiver RDT mistrust, demand for certain drugs, and desire to know the ‘exact’ disease cause if not malaria. Many health workers expressed uncertainty about how to manage non-malaria pediatric fevers, feared doing wrong and patient death, worried caregivers would lose trust, or felt unsatisfied without a clear diagnosis. Conclusions: Enhanced support is needed to improve RDT adoption at lower level clinics that focuses on empowering providers to successfully manage non-severe non-malaria pediatric fevers without referral. This includes building trust in negative results, reinforcing integrated care initiatives (e.g. Integrated Management of Childhood Illness) and fostering communities of practice according to the Diffusion of Innovation model.
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| 6. |
- Kitahara, Cari M., et al.
(författare)
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Anthropometric Factors and Thyroid Cancer Risk by Histological Subtype : Pooled Analysis of 22 Prospective Studies
- 2016
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Ingår i: Thyroid. - : MARY ANN LIEBERT, INC. - 1050-7256 .- 1557-9077. ; 26:2, s. 306-318
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Tidskriftsartikel (refereegranskat)abstract
- Background: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality. Methods: This large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information. Results: During follow-up, 2996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: hazard ratios (HR) [confidence intervals (CIs)] for height (per 5cm)=1.07 [1.04-1.10], BMI (per 5kg/m(2))=1.06 [1.02-1.10], waist circumference (per 5cm)=1.03 [1.01-1.05], young-adult BMI (per 5kg/m(2))=1.13 [1.02-1.25], and adulthood BMI gain (per 5kg/m(2))=1.07 [1.00-1.15]. Associations for baseline BMI and waist circumference were attenuated after mutual adjustment. Baseline BMI was more strongly associated with risk in men compared with women (p=0.04). Positive associations were observed for papillary, follicular, and anaplastic, but not medullary, thyroid carcinomas. Similar, but stronger, associations were observed for thyroid cancer mortality. Conclusion: The results suggest that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but most aggressive form, anaplastic carcinoma, and higher thyroid cancer mortality. Potential underlying biological mechanisms should be explored in future studies.
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| 7. |
- Machiela, Mitchell J, et al.
(författare)
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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| 8. |
- Wentzensen, Nicolas, et al.
(författare)
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Ovarian Cancer Risk Factors by Histologic Subtype : An Analysis From the Ovarian Cancer Cohort Consortium
- 2016
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Ingår i: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 34:24, s. 2888-2898
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3).Patients and Methods: Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test.Results: Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas.Conclusion: The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype.
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| 9. |
- Zhang, Mingfeng, et al.
(författare)
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Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:41, s. 66328-66343
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10(-15)), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10(-9)) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10(-8)). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L-TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10(-8)). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10(-4)-2.0x10(-3)). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
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