| 161. |
- O'Reilly, Kathleen M., et al.
(författare)
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Projecting the end of the Zika virus epidemic in Latin America : a modelling analysis
- 2018
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Zika virus (ZIKV) emerged in Latin America and the Caribbean (LAC) region in 2013, with serious implications for population health in the region. In 2016, the World Health Organization declared the ZIKV outbreak a Public Health Emergency of International Concern following a cluster of associated neurological disorders and neonatal malformations. In 2017, Zika cases declined, but future incidence in LAC remains uncertain due to gaps in our understanding, considerable variation in surveillance and the lack of a comprehensive collation of data from affected countries.Methods: Our analysis combines information on confirmed and suspected Zika cases across LAC countries and a spatio-temporal dynamic transmission model for ZIKV infection to determine key transmission parameters and projected incidence in 90 major cities within 35 countries. Seasonality was determined by spatio-temporal estimates of Aedes aegypti vectorial capacity. We used country and state-level data from 2015 to mid-2017 to infer key model parameters, country-specific disease reporting rates, and the 2018 projected incidence. A 10-fold cross-validation approach was used to validate parameter estimates to out-of-sample epidemic trajectories.Results: There was limited transmission in 2015, but in 2016 and 2017 there was sufficient opportunity for wide-spread ZIKV transmission in most cities, resulting in the depletion of susceptible individuals. We predict that the highest number of cases in 2018 would present within some Brazilian States (Sao Paulo and Rio de Janeiro), Colombia and French Guiana, but the estimated number of cases were no more than a few hundred. Model estimates of the timing of the peak in incidence were correlated (p < 0.05) with the reported peak in incidence. The reporting rate varied across countries, with lower reporting rates for those with only confirmed cases compared to those who reported both confirmed and suspected cases.Conclusions: The findings suggest that the ZIKV epidemic is by and large over within LAC, with incidence projected to be low in most cities in 2018. Local low levels of transmission are probable, but the estimated rate of infection suggests that most cities have a population with high levels of herd immunity.
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| 162. |
- Ottosson, Filip, et al.
(författare)
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Unraveling the metabolomic architecture of autism in a large Danish population-based cohort
- 2024
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Ingår i: BMC Medicine. - 1741-7015. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of autism in Denmark has been increasing, reaching 1.65% among 10-year-old children, and similar trends are seen elsewhere. Although there are several factors associated with autism, including genetic, environmental, and prenatal factors, the molecular etiology of autism is largely unknown. Here, we use untargeted metabolomics to characterize the neonatal metabolome from dried blood spots collected shortly after birth. Methods: We analyze the metabolomic profiles of a subset of a large Danish population-based cohort (iPSYCH2015) consisting of over 1400 newborns, who later are diagnosed with autism and matching controls and in two Swedish population-based cohorts comprising over 7000 adult participants. Mass spectrometry analysis was performed by a timsTOF Pro operated in QTOF mode, using data-dependent acquisition. By applying an untargeted metabolomics approach, we could reproducibly measure over 800 metabolite features. Results: We detected underlying molecular perturbations across several metabolite classes that precede autism. In particular, the cyclic dipeptide cyclo-leucine-proline (FDR-adjusted p = 0.003) and the carnitine-related 5-aminovaleric acid betaine (5-AVAB) (FDR-adjusted p = 0.03), were associated with an increased probability for autism, independently of known prenatal and genetic risk factors. Analysis of genetic and dietary data in adults revealed that 5-AVAB was associated with increased habitual dietary intake of dairy (FDR-adjusted p < 0.05) and with variants near SLC22A4 and SLC22A5 (p < 5.0e − 8), coding for a transmembrane carnitine transporter protein involved in controlling intracellular carnitine levels. Conclusions: Cyclo-leucine-proline and 5-AVAB are associated with future diagnosis of autism in Danish neonates, both representing novel early biomarkers for autism. 5-AVAB is potentially modifiable and may influence carnitine homeostasis.
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| 163. |
- Perez-Cornago, Aurora, et al.
(författare)
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Tall height and obesity are associated with an increased risk of aggressive prostate cancer : results from the EPIC cohort study
- 2017
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relationship between body size and prostate cancer risk, and in particular risk by tumour characteristics, is not clear because most studies have not differentiated between high-grade or advanced stage tumours, but rather have assessed risk with a combined category of aggressive disease. We investigated the association of height and adiposity with incidence of and death from prostate cancer in 141,896 men in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Multivariable-adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average of 13.9 years of follow-up, there were 7024 incident prostate cancers and 934 prostate cancer deaths. Results: Height was not associated with total prostate cancer risk. Subgroup analyses showed heterogeneity in the association with height by tumour grade (P-heterogeneity = 0.002), with a positive association with risk for high-grade but not low-intermediate-grade disease (HR for high-grade disease tallest versus shortest fifth of height, 1.54; 95% CI, 1.18-2.03). Greater height was also associated with a higher risk for prostate cancer death (HR = 1.43, 1.14-1.80). Body mass index (BMI) was significantly inversely associated with total prostate cancer, but there was evidence of heterogeneity by tumour grade (P-heterogeneity = 0.01; HR = 0.89, 0.79-0.99 for low-intermediate grade and HR = 1.32, 1.01-1.72 for high-grade prostate cancer) and stage (P-heterogeneity = 0.01; HR = 0.86, 0.75-0.99 for localised stage and HR = 1.11, 0.92-1.33 for advanced stage). BMI was positively associated with prostate cancer death (HR = 1.35, 1.09-1.68). The results for waist circumference were generally similar to those for BMI, but the associations were slightly stronger for high-grade (HR = 1.43, 1.07-1.92) and fatal prostate cancer (HR = 1.55, 1.23-1.96). Conclusions: The findings from this large prospective study show that men who are taller and who have greater adiposity have an elevated risk of high-grade prostate cancer and prostate cancer death.
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| 164. |
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| 165. |
- Rastogi, Simran, et al.
(författare)
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Fluorescence-tagged salivary small extracellular vesicles as a nanotool in early diagnosis of Parkinson’s disease
- 2023
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Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson’s disease is generally asymptomatic at earlier stages. At an early stage, there is an extensive progression in the neuropathological hallmarks, although, at this stage, diagnosis is not possible with currently available diagnostic methods. Therefore, the pressing need is for susceptibility risk biomarkers that can aid in better diagnosis and therapeutics as well can objectively serve to measure the endpoint of disease progression. The role of small extracellular vesicles (sEV) in the progression of neurodegenerative diseases could be potent in playing a revolutionary role in biomarker discovery.Methods: In our study, the salivary sEV were efficiently isolated by chemical precipitation combined with ultrafiltration from subjects (PD = 70, healthy controls = 26, and prodromal PD = 08), followed by antibody-based validation with CD63, CD9, GAPDH, Flotillin-1, and L1CAM. Morphological characterization of the isolated sEV through transmission electron microscopy. The quantification of sEV was achieved by fluorescence (lipid-binding dye-labeled) nanoparticle tracking analysis and antibody-based (CD63 Alexa fluor 488 tagged sEV) nanoparticle tracking analysis. The total alpha-synuclein (α-synTotal) in salivary sEVs cargo was quantified by ELISA. The disease severity staging confirmation for n = 18 clinically diagnosed Parkinson’s disease patients was done by 99mTc-TRODAT-single-photon emission computed tomography.Results: We observed a significant increase in total sEVs concentration in PD patients than in the healthy control (HC), where fluorescence lipid-binding dye-tagged sEV were observed to be higher in PD (p = 0.0001) than in the HC using NTA with a sensitivity of 94.34%. In the prodromal PD cases, the fluorescence lipid-binding dye-tagged sEV concentration was found to be higher (p = 0.008) than in HC. This result was validated through anti-CD63 tagged sEV (p = 0.0006) with similar sensitivity of 94.12%. We further validated our findings with the ELISA based on α-synTotal concentration in sEV, where it was observed to be higher in PD (p = 0.004) with a sensitivity of 88.24%. The caudate binding ratios in 99mTc-TRODAT-SPECT represent a positive correlation with sEV concentration (r = 0.8117 with p = 0.0112).Conclusions: In this study, for the first time, we have found that the fluorescence-tagged sEV has the potential to screen the progression of disease with clinically acceptable sensitivity and can be a potent early detection method for PD.
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| 166. |
- Rehm, Jürgen, et al.
(författare)
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Acceptable risk? : Why does society accept a higher risk for alcohol than for other voluntary or involuntary risks?
- 2014
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 12, s. 189-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Societies tend to accept much higher risks for voluntary behaviours, those based on individualdecisions (for example, to smoke, to consume alcohol, or to ski), than for involuntary exposure such as exposure torisks in soil, drinking water or air. In high-income societies, an acceptable risk to those voluntarily engaging in a riskybehaviour seems to be about one death in 1,000 on a lifetime basis. However, drinking more than 20 g purealcohol per day over an adult lifetime exceeds a threshold of one in 100 deaths, based on a calculation from WorldHealth Organization data of the odds in six European countries of dying from alcohol-attributable causes at differentlevels of drinking.Discussion: The voluntary mortality risk of alcohol consumption exceeds the risks of other lifestyle risk factors. Inaddition, evidence shows that the involuntary risks resulting from customary alcohol consumption far exceed theacceptable threshold for other involuntary risks (such as those established by the World Health Organization ornational environmental agencies), and would be judged as not acceptable. Alcohol’s exceptional status reflectsvagaries of history, which have so far resulted in alcohol being exempted from key food legislation (no labelling ofingredients and nutritional information) and from international conventions governing all other psychoactivesubstances (both legal and illegal). This is along with special treatment of alcohol in the public health field, in partreflecting overestimation of its beneficial effect on ischaemic disease when consumed in moderation.Summary: A much higher mortality risk from alcohol than from other risk factors is currently accepted by highincome countries.
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| 167. |
- Rehm, Jürgen, et al.
(författare)
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Towards new recommendations to reduce the burden of alcohol-induced hypertension in the European Union
- 2017
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHazardous and harmful alcohol use and high blood pressure are central risk factors related to premature non-communicable disease (NCD) mortality worldwide. A reduction in the prevalence of both risk factors has been suggested as a route to reach the global NCD targets. This study aims to highlight that screening and interventions for hypertension and hazardous and harmful alcohol use in primary healthcare can contribute substantially to achieving the NCD targets.MethodsA consensus conference based on systematic reviews, meta-analyses, clinical guidelines, experimental studies, and statisticalmodelling which had been presented and discussed in five preparatory meetings, was undertaken. Specifically, we modelled changes in blood pressure distributions and potential lives saved for the five largest European countries if screening and appropriate intervention rates in primary healthcare settings were increased. Recommendations to handle alcohol-induced hypertension in primary healthcare settings were derived at the conference, and their degree of evidence was graded.ResultsScreening and appropriate interventions for hazardous alcohol use and use disorders could lower blood pressure levels, but there is a lack in implementing these measures in European primary healthcare. Recommendations included (1) an increase in screening for hypertension (evidence grade: high), (2) an increase in screening and brief advice on hazardous and harmful drinking for people with newly detected hypertension by physicians, nurses, and other healthcare professionals (evidence grade: high), (3) the conduct of clinical management of less severe alcohol use disorders for incident people with hypertension in primary healthcare (evidence grade: moderate), and (4) screening for alcohol use in hypertension that is not well controlled (evidence grade: moderate). The first three measures were estimated to result in a decreased hypertension prevalence and hundreds of saved lives annually in the examined countries.ConclusionsThe implementation of the outlined recommendations could contribute to reducing the burden associated with hypertension and hazardous and harmful alcohol use and thus to achievement of the NCD targets. Implementation should be conducted in controlled settings with evaluation, including, but not limited to, economic evaluation.
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| 168. |
- Riemsma, R., et al.
(författare)
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Can incontinence be cured? A systematic review of cure rates
- 2017
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Ingår i: Bmc Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 15:63
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Tidskriftsartikel (refereegranskat)abstract
- Background: Incontinence constitutes a major health problem affecting millions of people worldwide. The present study aims to assess cure rates from treating urinary (UI) or fecal incontinence (FI) and the number of people who may remain dependent on containment strategies. Methods: Medline, Embase, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, and PEDro were searched from January 2005 to June 2015. Supplementary searches included conference abstracts and trials registers (2013-2015). Included studies had patients >= 18 years with UI or FI, reported treatment cure or success rates, had >= 50 patients treated with any intervention recognized in international guideline algorithms, a followup >= 3 months, and were published from 2005 onwards. Title and abstract screening, full paper screening, data extraction and risk-of-bias assessment were performed independently by two reviewers. Disagreements were resolved through discussion or referral to a third reviewer where necessary. A narrative summary of included studies is presented. Results: Most evidence was found for UI: Surgical interventions for stress UI showed a median cure rate of 82.3% (interquartile range (IQR), 72-89.5%); people with urgency UI were mostly treated using medications ( median cure rate for antimuscarinics = 49%; IQR, 35.6-58%). Pelvic floor muscle training and bulking agents showed lower cure rates for UI. Sacral neuromodulation for FI had a median cure rate of 38.6% (IQR, 35.6-40.6%). Conclusions: Many individuals were not cured and hence may continue to rely on containment. No studies were found assessing success of containment strategies. There was a lack of data in the disabled and in those with neurological diseases, in the elderly and those with cognitive impairment. Surgical interventions were effective for stress UI. Other interventions for UI and FI showed lower cure rates. Many individuals are likely to be reliant on containment strategies.
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| 169. |
- Romaguera, Dora, et al.
(författare)
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Pre-diagnostic concordance with the WCRF/AICR guidelines and survival in European colorectal cancer patients : a cohort study
- 2015
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients.METHODS: The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality.RESULTS: The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend <0.0001), compared to participants with the lowest concordance with the recommendations (category 1 of the score: 0-2/0-3). Similar HRs for overall mortality were observed (P for trend 0.004). Meeting the recommendations on body fatness and plant food consumption were associated with improved survival among CRC cases in mutually adjusted models.CONCLUSIONS: Greater concordance with the WCRF/AICR recommendations on diet, physical activity, and body fatness prior to CRC diagnosis is associated with improved survival among CRC patients.
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