PLoS medicine
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Multicenter Study Comparative Study
Gene-environment interaction in the onset of eczema in infancy: filaggrin loss-of-function mutations enhanced by neonatal cat exposure.
Loss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites) in relation to the development of eczema. ⋯ We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4) and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially increases the risk of eczema within the first year of life in children with FLG loss-of-function variants, but not amongst those without. FLG-deficient individuals may need to avoid cats but not dogs in early life.
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Randomized Controlled Trial Multicenter Study
A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial).
There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease. ⋯ For most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on functional and cognitive status. Neuroleptics may have some value in the maintenance treatment of more severe neuropsychiatric symptoms, but this benefit must be weighed against the side effects of therapy.
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Multicenter Study
Clustered environments and randomized genes: a fundamental distinction between conventional and genetic epidemiology.
In conventional epidemiology confounding of the exposure of interest with lifestyle or socioeconomic factors, and reverse causation whereby disease status influences exposure rather than vice versa, may invalidate causal interpretations of observed associations. Conversely, genetic variants should not be related to the confounding factors that distort associations in conventional observational epidemiological studies. Furthermore, disease onset will not influence genotype. Therefore, it has been suggested that genetic variants that are known to be associated with a modifiable (nongenetic) risk factor can be used to help determine the causal effect of this modifiable risk factor on disease outcomes. This approach, mendelian randomization, is increasingly being applied within epidemiological studies. However, there is debate about the underlying premise that associations between genotypes and disease outcomes are not confounded by other risk factors. We examined the extent to which genetic variants, on the one hand, and nongenetic environmental exposures or phenotypic characteristics on the other, tend to be associated with each other, to assess the degree of confounding that would exist in conventional epidemiological studies compared with mendelian randomization studies. ⋯ These data illustrate why observational studies have produced misleading claims regarding potentially causal factors for disease. The findings demonstrate the potential power of a methodology that utilizes genetic variants as indicators of exposure level when studying environmentally modifiable risk factors.
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Multicenter Study
Determinants of treatment adherence among smear-positive pulmonary tuberculosis patients in Southern Ethiopia.
Defaulting from treatment remains a challenge for most tuberculosis control programmes. It may increase the risk of drug resistance, relapse, death, and prolonged infectiousness. The aim of this study was to determine factors predicting treatment adherence among smear-positive pulmonary tuberculosis patients. ⋯ Defaulting due to treatment noncompletion in this study setting is high, and the main determinants appear to be factors related to physical access to a treatment centre. The continuation phase of treatment is the most crucial time for treatment interruption, and future interventions should take this factor into consideration.
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Multicenter Study
Determinants of disease presentation and outcome during cryptococcosis: the CryptoA/D study.
Cryptococcosis is a life-threatening opportunistic fungal infection in both HIV-positive and -negative patients. Information on clinical presentation and therapeutic guidelines, derived mostly from clinical trials performed before introduction of highly active antiretroviral therapy in patients with cryptococcal meningoencephalitis, is missing data on extrameningeal involvement and infections by serotype D as opposed to serotype A of Cryptococcus neoformans. ⋯ Thus sex, HIV status, and infecting serotype are major determinants of presentation and outcome during cryptococcosis. We propose a modification of current guidelines for the initial management of cryptococcosis based on systematic fungal burden evaluation.