Episodes of acute infection are thought to deplete body stores of vitamin A. The mechanism by which this might occur is not known, but increased metabolic requirements are presumed to play a role. We have found, however, that significant amounts of retinol and retinol-binding protein (RBP) were excreted in the urine during serious infections, whereas only trace amounts were found in the urine of healthy control subjects. The geometric mean excretion rate in 29 subjects with pneumonia and sepsis was 0.78 mumol retinol/d. Subjects with fever (temperature > or = 38.3 degrees C) excreted significantly more retinol (geometric mean = 1.67 mumol/d) than did those without fever (0.18 mumol/d; t = 3.53, P < 0.0015). Aminoglycoside administration and low glomerular filtration rates (< 35 mL/min) were also associated with higher rates of urinary retinol excretion. Thirty-four percent of patients excreted > 1.75 mumol retinol/d, equivalent to 50% of the US recommended dietary allowance. These data show that vitamin A requirements are substantially increased during serious infections because of excretion of retinol in the urine, and suggest that these losses are due to pathologic changes associated with the febrile response.

IntroductionAminoglycosides aerosolization might achieve better diffusion into the alveolar compartment than intravenous use. The objective of this multicenter study was to evaluate aerosol-delivered amikacin penetration into the alveolar epithelial lining fluid (ELF) using a new vibrating mesh nebulizer (Pulmonary Drug Delivery System (PDDS), Nektar Therapeutics), which delivers high doses to the lungs.MethodsNebulized amikacin (400 mg bid) was delivered to the lungs of 28 mechanically ventilated patients with Gram-negative VAP for 7-14 days, adjunctive to intravenous therapy. On treatment day 3, 30 minutes after completing aerosol delivery, all the patients underwent bronchoalveolar lavage in the infection-involved area and the ELF amikacin concentration was determined. The same day, urine and serum amikacin concentrations were determined at different time points.ResultsMedian (range) ELF amikacin and maximum serum amikacin concentrations were 976.1 (135.7-16127.6) and 0.9 (0.62-1.73) μg/mL, respectively. The median total amount of amikacin excreted in urine during the first and second 12-hour collection on day 3 were 19 (12.21-28) and 21.2 (14.1-29.98) μg, respectively. During the study period, daily through amikacin measurements were below the level of nephrotoxicity. Sixty-four unexpected adverse events were reported, among which 2 were deemed possibly due to nebulized amikacin: one episode of worsening renal failure, and one episode of bronchospasm.ConclusionsPDDS delivery of aerosolized amikacin achieved very high aminoglycoside concentrations in ELF from radiography-controlled infection-involved zones, while maintaining safe serum amikacin concentrations. The ELF concentrations always exceeded the amikacin minimum inhibitory concentrations for Gram-negative microorganisms usually responsible for these pneumonias. The clinical impact of amikacin delivery with this system remains to be determined.Trial RegistrationClinicalTrials.gov Identifier: NCT01021436.

ObjectiveDespite multiple published studies regarding the association between formaldehyde exposure and childhood asthma, a consistent association has not been identified. Here we report the results of a systematic review of published literature in order to provide a more comprehensive picture of this relationship.Data sourcesAfter a comprehensive literature search, we identified seven peer-reviewed studies providing quantitative results regarding the association between formaldehyde exposure and asthma in children. Studies were heterogeneous with respect to the definition of asthma (e.g., self-report, physician diagnosis). Most of the studies were cross-sectional.Data extractionFor each study, an odds ratio (OR) and 95% confidence interval (CI) for asthma were either abstracted from published results or calculated based on the data provided. Characteristics regarding the study design and population were also abstracted.Data synthesisWe used fixed- and random-effects models to calculate pooled ORs and 95% CIs; measures of heterogeneity were also calculated. A fixed-effects model produced an OR of 1.03 (95% CI, 1.02–1.04), and random effects model produced an OR of 1.17 (95% CI, 1.01–1.36), both reflecting an increase of 10 μg/m3 of formaldehyde. Both the Q and I2 statistics indicated a moderate amount of heterogeneity.ConclusionsResults indicate a significant positive association between formaldehyde exposure and childhood asthma. Given the largely cross-sectional nature of the studies underlying this meta-analysis, further well-designed prospective epidemiologic studies are needed.

Formaldehyde exposure and asthma in children: a systematic review Exposição ao formol e asma em crianças: uma revisão sistemáticaResumo Apesar de múltiplos estudos publicados sobre a associação entre exposição ao formol e asma infantil, uma relação consistente ainda não foi identificada. Nós relacionamos os resultados de revisão de estudos publicados a fim de fornecer uma imagem mais compreensível desta relação. Após pesquisa, foram identificados sete estudos que proviam resultados quantitativos sobre a associação entre a exposição ao formol e a asma infantil. Estudos foram heterogêneos em relação à definição de asma. Para cada estudo, uma razão de chances (RC) e 95% de intervalo de confiança (IC) para asma foram abstraídos de resultados publicados ou calculados baseados nos dados fornecidos. Foram usados modelos de efeitos fixos e aleatórios para calcular RC agrupados e IC de 95%; medidas de heterogeneidade também foram calculadas. Um modelo de efeitos fixos produziu um a RC de 1.03 (IC de 95%, 1.02-1.04), e o modelo de efeitos aleatórios produziu uma RC de 1.17 (IC de 95%, 1.01-1.36), ambos refletindo um aumento de 10 μg/m3 de exposição ao formol. As estatís-ticas de Q and I2 indicaram uma quantidade moderada de heterogeneidade. Resultados indicam uma associação positiva entre exposição ao formol e asma infantil. Devido à natureza de cruzamento de dados destes estudos por baixo desta meta-análise, um estudo de prospectiva epidemiológica mais aprofundada é necessário. Palavras-chave Asma, Crianças, Epidemiologia, Formol Abstract Despite multiple published studies regarding the association between formaldehyde exposure and childhood asthma, a consistent association has not been identified. Here we report the results of a systematic review of published literature in order to provide a more comprehensive picture of this relationship. After a literature search, we identified seven studies providing quantitative results regarding the association between formaldehyde exposure and asthma in children. Studies were heterogeneous with respect to the definition of asthma. For each study, an odds ratio (OR) and 95% confidence interval (CI) for asthma were abstracted from published results or calculated based on the data provided. We used fixed-and random-effects models to calculate pooled ORs and 95% CIs; measures of heterogeneity were also calculated. A fixed-effects model produced an OR of 1.03 (95% CI, 1.02-1.04), and random effects model produced an OR of 1.17 (95% CI, 1.01-1.36), both reflecting an increase of 10 μg/m3 of formaldehyde. Both the Q and I2 statistics indicated a moderate amount of heterogeneity. Results indicate a positive association between formaldehyde exposure and childhood asthma. Given the largely cross-sectional nature of the studies underlying this meta-analysis, further well-designed prospective epidemiologic studies are needed.

PARTICIPANTS provided with a PDA-based CDSS for NSAID prescribing made fewer unsafe treatment decisions than participants without the CDSS.

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