| 1. |
- Baldeh, Tejan, et al.
(author)
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Development and use of health outcome descriptors : a guideline development case study
- 2020
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In: Health and Quality of Life Outcomes. - : BioMed Central. - 1477-7525 .- 1477-7525. ; 18:1
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Journal article (peer-reviewed)abstract
- Background: During healthcare guideline development, panel members often have implicit, different definitions of health outcomes that can lead to misunderstandings about how important these outcomes are and how to balance benefits and harms. McMaster GRADE Centre researchers developed ‘health outcome descriptors’ for standardizing descriptions of health outcomes and overcoming these problems to support the European Commission Initiative on Breast Cancer (ECIBC) Guideline Development Group (GDG). We aimed to determine which aspects of the development, content, and use of health outcome descriptors were valuable to guideline developers.Methods: We developed 24 health outcome descriptors related to breast cancer screening and diagnosis for the European Commission Breast Guideline Development Group (GDG). Eighteen GDG members provided feedback in written format or in interviews. We then evaluated the process and conducted two health utility rating surveys.Results: Feedback from GDG members revealed that health outcome descriptors are probably useful for developing recommendations and improving transparency of guideline methods. Time commitment, methodology training, and need for multidisciplinary expertise throughout development were considered important determinants of the process. Comparison of the two health utility surveys showed a decrease in standard deviation in the second survey across 21 (88%) of the outcomes.Conclusions: Health outcome descriptors are feasible and should be developed prior to the outcome prioritization step in the guideline development process. Guideline developers should involve a subgroup of multidisciplinary experts in all stages of development and ensure all guideline panel members are trained in guideline methodology that includes understanding the importance of defining and understanding the outcomes of interest.
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| 2. |
- Chirambo, Griphin Baxter, et al.
(author)
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Effectiveness of Smartphone-Based Community Case Management on the Urgent Referral, Reconsultation, and Hospitalization of Children Aged Under 5 Years in Malawi : Cluster-Randomized, Stepped-Wedge Trial
- 2021
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In: Journal of Medical Internet Research. - : JMIR Publications. - 1438-8871. ; 23:10
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Journal article (peer-reviewed)abstract
- BACKGROUND: Integrated community case management (CCM) has led to reductions in child mortality in Malawi resulting from illnesses such as malaria, pneumonia, and diarrhea. However, adherence to CCM guidelines is often poor, potentially leading to inappropriate clinical decisions and poor outcomes. We determined the impact of an e-CCM app on the referral, reconsultation, and hospitalization rates of children presenting to village clinics in Malawi.OBJECTIVE: We determined the impact of an electronic version of a smartphone-based CCM (e-CCM) app on the referral, reconsultation, and hospitalization rates of children presenting to village clinics in Malawi.METHODS: We used a stepped-wedge, cluster-randomized trial to compare paper-based CCM (control) with and without the use of an e-CCM app on smartphones from November 2016 to February 2017. A total of 102 village clinics from 2 districts in northern Malawi were assigned to 1 of 6 clusters, which were randomized on the sequencing of the crossover from the control phase to the intervention phase as well as the duration of exposure in each phase. Children aged ≥2 months to <5 years who presented with acute illness were enrolled consecutively by health surveillance assistants. The primary outcome of urgent referrals to higher-level facilities was evaluated by using multilevel mixed effects models. A logistic regression model with the random effects of the cluster and the fixed effects for each step was fitted. The adjustment for potential confounders included baseline factors, such as patient age, sex, and the geographical location of the village clinics. Calendar time was adjusted for in the analysis.RESULTS: A total of 6965 children were recruited-49.11% (3421/6965) in the control phase and 50.88% (3544/6965) in the intervention phase. After adjusting for calendar time, children in the intervention phase were more likely to be urgently referred to a higher-level health facility than children in the control phase (odds ratio [OR] 2.02, 95% CI 1.27-3.23; P=.003). Overall, children in the intervention arm had lower odds of attending a repeat health surveillance assistant consultation (OR 0.45, 95% CI 0.34-0.59; P<.001) or being admitted to a hospital (OR 0.75, 95% CI 0.62-0.90; P=.002), but after adjusting for time, these differences were not significant (P=.07 for consultation; P=.30 for hospital admission).CONCLUSIONS: The addition of e-CCM decision support by using smartphones led to a greater proportion of children being referred to higher-level facilities, with no apparent increase in hospital admissions or repeat consultations in village clinics. Our findings provide support for the implementation of e-CCM tools in Malawi and other low- and middle-income countries with a need for ongoing assessments of effectiveness and integration with national digital health strategies.TRIAL REGISTRATION: ClinicalTrials.gov NCT02763345; https://clinicaltrials.gov/ct2/show/NCT02763345.
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| 3. |
- Escott-Price, Valentina, et al.
(author)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Journal article (peer-reviewed)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 4. |
- Ewers, Michael, et al.
(author)
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Body mass index is associated with biological CSF markers of core brain pathology of Alzheimer's disease
- 2012
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In: Neurobiology of Aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 33:8, s. 1599-1608
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Journal article (peer-reviewed)abstract
- Weight changes are common in aging and Alzheimer's disease (AD) and postmortem findings suggest a relation between lower body mass index (BMI) and increased AD brain pathology. In the current multicenter study, we tested whether lower BMI is associated with higher core AD brain pathology as assessed by cerebrospinal fluid (CSF)-based biological markers of AD in 751 living subjects: 308 patients with AD, 296 subjects with amnestic mild cognitive impairment (MCI), and 147 elderly healthy controls (HC). Based upon a priori cutoff values on CSF concentration of total tau and beta-amyloid (A beta(1-42)), subjects were binarized into a group with abnormal CSF biomarker signature (CSF+) and those without (CSF-). Results showed that BMI was significantly lower in the CSF+ when compared with the CSF- group (F = 27.7, df = 746, p < 0.001). There was no interaction between CSF signature and diagnosis or apolipoprotein E (ApoE) genotype. In conclusion, lower BMI is indicative of AD pathology as assessed with CSF-based biomarkers in demented and nondemented elderly subjects. Published by Elsevier Inc.
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| 5. |
- Hardy, Victoria, et al.
(author)
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The added value of a mobile application of Community Case Management on referral, re-consultation and hospitalization rates of children aged under 5 years in two districts in Northern Malawi : study protocol for a pragmatic, stepped-wedge cluster-randomized controlled trial
- 2017
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In: Trials. - : BioMed Central. - 1745-6215. ; 18:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: There is evidence to suggest that frontline community health workers in Malawi are under-referring children to higher-level facilities. Integrating a digitized version of paper-based methods of Community Case Management (CCM) could strengthen delivery, increasing urgent referral rates and preventing unnecessary re-consultations and hospital admissions. This trial aims to evaluate the added value of the Supporting LIFE electronic Community Case Management Application (SL eCCM App) compared to paper-based CCM on urgent referral, re-consultation and hospitalization rates, in two districts in Northern Malawi.METHODS/DESIGN: This is a pragmatic, stepped-wedge cluster-randomized trial assessing the added value of the SL eCCM App on urgent referral, re-consultation and hospitalization rates of children aged 2 months and older to up to 5 years, within 7 days of the index visit. One hundred and two health surveillance assistants (HSAs) were stratified into six clusters based on geographical location, and clusters randomized to the timing of crossover to the intervention using simple, computer-generated randomization. Training workshops were conducted prior to the control (paper-CCM) and intervention (paper-CCM + SL eCCM App) in assigned clusters. Neither participants nor study personnel were blinded to allocation. Outcome measures were determined by abstraction of clinical data from patient records 2 weeks after recruitment. A nested qualitative study explored perceptions of adherence to urgent referral recommendations and a cost evaluation determined the financial and time-related costs to caregivers of subsequent health care utilization. The trial was conducted between July 2016 and February 2017.DISCUSSION: This is the first large-scale trial evaluating the value of adding a mobile application of CCM to the assessment of children aged under 5 years. The trial will generate evidence on the potential use of mobile health for CCM in Malawi, and more widely in other low- and middle-income countries.TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02763345 . Registered on 3 May 2016.
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| 6. |
- Jakobsdottir, Johanna, et al.
(author)
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Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease
- 2016
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In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:10
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Journal article (peer-reviewed)abstract
- We performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (similar to 0.5% versus < 0.05% in other European populations). In 433 LOAD cases and 3903 controls from the Icelandic AGES substudy, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI) = 7.5 (3.5-15.9), p = 6.6x10(-9)]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the beta-amyloid cascade.
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| 7. |
- Jones, Lesley, et al.
(author)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Journal article (peer-reviewed)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 8. |
- Muratov, Sergei, et al.
(author)
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Monitoring and evaluation of breast cancer screening programmes : selecting candidate performance indicators
- 2020
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In: BMC Cancer. - : BioMed Central. - 1471-2407 .- 1471-2407. ; 20:1
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Journal article (peer-reviewed)abstract
- Background: In the scope of the European Commission Initiative on Breast Cancer (ECIBC) the Monitoring and Evaluation (M&E) subgroup was tasked to identify breast cancer screening programme (BCSP) performance indicators, including their acceptable and desirable levels, which are associated with breast cancer (BC) mortality. This paper documents the methodology used for the indicator selection.Methods: The indicators were identified through a multi-stage process. First, a scoping review was conducted to identify existing performance indicators. Second, building on existing frameworks for making well-informed health care choices, a specific conceptual framework was developed to guide the indicator selection. Third, two group exercises including a rating and ranking survey were conducted for indicator selection using pre-determined criteria, such as: relevance, measurability, accurateness, ethics and understandability. The selected indicators were mapped onto a BC screening pathway developed by the M&E subgroup to illustrate the steps of BC screening common to all EU countries.Results: A total of 96 indicators were identified from an initial list of 1325 indicators. After removing redundant and irrelevant indicators and adding those missing, 39 candidate indicators underwent the rating and ranking exercise. Based on the results, the M&E subgroup selected 13 indicators: screening coverage, participation rate, recall rate, breast cancer detection rate, invasive breast cancer detection rate, cancers >20mm, cancers <= 10mm, lymph node status, interval cancer rate, episode sensitivity, time interval between screening and first treatment, benign open surgical biopsy rate, and mastectomy rate.Conclusion: This systematic approach led to the identification of 13 BCSP candidate performance indicators to be further evaluated for their association with BC mortality.
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| 9. |
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| 10. |
- Schunemann, Holger J., et al.
(author)
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Breast Cancer Screening and Diagnosis : A Synopsis of the European Breast Guidelines
- 2020
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In: Annals of Internal Medicine. - : Amer Coll Physicians. - 0003-4819 .- 1539-3704. ; 172:1, s. 46-56
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Journal article (peer-reviewed)abstract
- Description: The European Commission Initiative for Breast Cancer Screening and Diagnosis guidelines (European Breast Guidelines) are coordinated by the European Commission's Joint Research Centre. The target audience for the guidelines includes women, health professionals, and policymakers.Methods: An international guideline panel of 28 multidisciplinary members, including patients, developed questions and corresponding recommendations that were informed by systematic reviews of the evidence conducted between March 2016 and December 2018. GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision frameworks were used to structure the process and minimize the influence of competing interests by enhancing transparency. Questions and recommendations, expressed as strong or conditional, focused on outcomes that matter to women and provided a rating of the certainty of evidence.Recommendations: This synopsis of the European Breast Guidelines provides recommendations regarding organized screening programs for women aged 40 to 75 years who are at average risk. The recommendations address digital mammography screening and the addition of hand-held ultrasonography, automated breast ultrasonography, or magnetic resonance imaging compared with mammography alone. The recommendations also discuss the frequency of screening and inform decision making for women at average risk who are recalled for suspicious lesions or who have high breast density.
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