| 41. |
- 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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| 42. |
- 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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| 43. |
- Johansson, Emily White, 1976-, et al.
(författare)
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Diagnostic Testing of Pediatric Fevers: Meta-Analysis of 13 National Surveys Assessing Influences of Malaria Endemicity and Source of Care on Test Uptake for Febrile Children under Five Years
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 2010, the World Health Organization revised guidelines to recommend diagnosis of all suspected malaria cases prior to treatment. There has been no systematic assessment of malaria test uptake for pediatric fevers at the population level as countries start implementing guidelines. We examined test use for pediatric fevers in relation to malaria endemicity and treatment-seeking behavior in multiple sub-Saharan African countries in initial years of implementation. Methods and Findings: We compiled data from national population-based surveys reporting fever prevalence, care-seeking and diagnostic use for children under five years in 13 sub-Saharan African countries in 2009-2011/12 (n = 105,791). Mixed-effects logistic regression models quantified the influence of source of care and malaria endemicity on test use after adjusting for socioeconomic covariates. Results were stratified by malaria endemicity categories: low (PfPR(2-10)<5%), moderate (PfPR(2-10) 5-40%), high (PfPR(2-10)>40%). Among febrile under-fives surveyed, 16.9% (95% CI: 11.8%-21.9%) were tested. Compared to hospitals, febrile children attending non-hospital sources (OR: 0.62, 95% CI: 0.56-0.69) and community health workers (OR: 0.31, 95% CI: 0.23-0.43) were less often tested. Febrile children in high-risk areas had reduced odds of testing compared to low-risk settings (OR: 0.51, 95% CI: 0.42-0.62). Febrile children in least poor households were more often tested than in poorest (OR: 1.63, 95% CI: 1.39-1.91), as were children with better-educated mothers compared to least educated (OR: 1.33, 95% CI: 1.16-1.54). Conclusions: Diagnostic testing of pediatric fevers was low and inequitable at the outset of new guidelines. Greater testing is needed at lower or less formal sources where pediatric fevers are commonly managed, particularly to reach the poorest. Lower test uptake in high-risk settings merits further investigation given potential implications for diagnostic scale-up in these areas. Findings could inform continued implementation of new guidelines to improve access to and equity in point-of-care diagnostics use for pediatric fevers.
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| 44. |
- Johansson, Emily White, 1976-, et al.
(författare)
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Effect of diagnostic testing on medicines used by febrile children less than five years in 12 malaria-endemic African countries: a mixed-methods study.
- 2015
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Ingår i: Malaria journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- In 2010, WHO revised guidelines to recommend testing all suspected malaria cases prior to treatment. Yet, evidence to assess programmes is largely derived from limited facility settings in a limited number of countries. National surveys from 12 sub-Saharan African countries were used to examine the effect of diagnostic testing on medicines used by febrile children under five years at the population level, including stratification by malaria risk, transmission season, source of care, symptoms, and age.
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| 45. |
- 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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| 46. |
- Johansson, Emily White, 1976-, et al.
(författare)
-
"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
-
Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875 .- 1475-2875. ; 15
-
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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| 47. |
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| 48. |
- Johansson, Mattias, et al.
(författare)
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The influence of obesity-related factors in the etiology of renal cell carcinoma—A mendelian randomization study
- 2019
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
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| 49. |
- Khankari, Nikhil K, et al.
(författare)
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Mendelian Randomization of Circulating Polyunsaturated Fatty Acids and Colorectal Cancer Risk.
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 29:4, s. 860-870
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Results from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin/NSAID use with PUFAs could help elucidate an association between PUFAs and colorectal cancer risk.METHODS: Information was leveraged from genome-wide association studies (GWAS) regarding PUFA-associated SNPs to create weighted genetic scores (wGS) representing genetically predicted circulating blood PUFAs for 11,016 non-Hispanic white colorectal cancer cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per SD increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on colorectal cancer risk were also examined.RESULTS: Modest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [ORLA = 0.96; 95% confidence interval (CI) = 0.93-0.98; P = 5.2 × 10-4] and α-linolenic acid (ORALA = 0.95; 95% CI = 0.92-0.97; P = 5.4 × 10-5), whereas modest increased risks were observed for arachidonic (ORAA = 1.06; 95% CI = 1.03-1.08; P = 3.3 × 10-5), eicosapentaenoic (OREPA = 1.04; 95% CI = 1.01-1.07; P = 2.5 × 10-3), and docosapentaenoic acids (ORDPA = 1.03; 95% CI = 1.01-1.06; P = 1.2 × 10-2). Each of these effects was stronger among aspirin/NSAID nonusers in the stratified analyses.CONCLUSIONS: Our study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced colorectal cancer risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased colorectal cancer risk.IMPACT: The interaction of PUFAs with aspirin/NSAID use indicates a shared colorectal cancer inflammatory pathway. Future research should continue to improve PUFA genetic instruments to elucidate the independent effects of PUFAs on colorectal cancer.
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| 50. |
- King, Sontoria D., et al.
(författare)
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Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization
- 2023
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 32:9, s. 1265-1269
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer. Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for pancreatic cancer.METHODS: Data from genome-wide association studies (GWAS) within the Pancreatic Cancer Cohort Consortium (PanScan; cases n = 5,090, controls n = 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n = 4,163, controls n = 3,792) were analyzed. We used data on 68 genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and pancreatic cancer risk, using logistic regression to calculate ORs and 95% confidence intervals (CI), adjusting for PC risk factors, including obesity and diabetes.RESULTS: No association was found between genetically predicted NAFLD and pancreatic cancer risk in the PanScan or PanC4 samples [e.g., PanScan, IVW OR, 1.04; 95% confidence interval (CI), 0.88-1.22; MR-Egger OR, 0.89; 95% CI, 0.65-1.21; PanC4, IVW OR, 1.07; 95% CI, 0.90-1.27; MR-Egger OR, 0.93; 95% CI, 0.67-1.28]. None of the four MR methods indicated an association between genetically predicted NAFLD and pancreatic cancer risk in either sample.CONCLUSIONS: Genetic predisposition to NAFLD is not associated with pancreatic cancer risk.IMPACT: Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and pancreatic cancer might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and pancreatic cancer.
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