The impact of prior outpatient ACE inhibitor use on 30-day mortality for patients hospitalized with community-acquired pneumonia

BACKGROUND: Recent studies suggest that angiotensin-converting enzyme (ACE) inhibitors may have beneficial effects for patients at risk for some types of infections. We examined the effect of prior outpatient use of ACE inhibitors on mortality for patients hospitalized with community-acquired pneumonia. METHODS: A retrospective cohort study conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had a chest x-ray consistent with, and had a discharge ICD-9 diagnosis of pneumonia. Subjects were excluded if they were "comfort measures only" or transferred from another acute care hospital. Subjects were considered to be on a medication if they were taking it at the time of presentation. RESULTS: Data was abstracted on 787 subjects at the two hospitals. Mortality was 9.2% at 30-days and 13.6% at 90-days. At presentation 52% of subjects were low risk, 34% were moderate risk, and 14% were high risk. In the multivariable conditional logistic regression analysis, after adjusting for potential confounders, the use of ACE inhibitors at presentation (odds ratio 0.44, 95% confidence interval 0.22–0.89) was significantly associated with 30-day mortality. CONCLUSION: Prior outpatient use of an ACE inhibitor was associated with decreased mortality in patients hospitalized with community-acquired pneumonia despite their use being associated with comorbid illnesses likely to contribute to increased mortality. Confirmatory studies are needed, as well as research to determine the mechanism(s) of this protective effect

TGF-β1 genotype and phenotype in breast cancer and their associations with IGFs and patient survival

Transforming growth factor-β (TGF-β)-mediated signals play complicated roles in the development and progression of breast tumour. The purposes of this study were to analyse the genotype of TGF-β1 at T29C and TGF-β1 phenotype in breast tumours, and to evaluate their associations with IGFs and clinical characteristics of breast cancer. Fresh tumour samples were collected from 348 breast cancer patients. TGF-β1 genotype and phenotype were analysed with TaqMan® and ELISA, respectively. Members of the IGF family in tumour tissue were measured with ELISA. Cox proportional hazards regression analysis was performed to assess the association of TGF-β1 and disease outcomes. Patients with the T/T (29%) genotype at T29C had the highest TGF-β1, 707.9 pg mg−1, followed by the T/C (49%), 657.8 pg mg−1, and C/C (22%) genotypes, 640.8 pg mg−1, (P=0.210, T/T vs C/C and C/T). TGF-β1 concentrations were positively correlated with levels of oestrogen receptor, IGF-I, IGF-II and IGFBP-3. Survival analysis showed TGF-β1 associated with disease progression, but the association differed by disease stage. For early-stage disease, patients with the T/T genotype or high TGF-β1 had shorter overall survival compared to those without T/T or with low TGF-β1; the hazard ratios (HR) were 3.54 (95% CI: 1.21–10.40) for genotype and 2.54 (95% CI: 1.10–5.89) for phenotype after adjusting for age, grade, histotype and receptor status. For late-stage disease, however, the association was different. The T/T genotype was associated with lower risk of disease recurrence (HR=0.13, 95% CI: 0.02–1.00), whereas no association was found between TGF-β1 phenotype and survival outcomes. The study suggests a complex role of TGF-β1 in breast cancer progression, which supports the finding of in vitro studies that TGF-β1 has conflicting effects on tumour growth and metastasis

Fostering teacher community development: A review of design principles and a case study of an innovative interdisciplinary team

To deal with recent reforms and the accompanying complexity of work in secondary education, ongoing collaboration between teachers has become more important. A community is seen as a promising learning environment to support and embed collaboration into the culture of the school. However, community theory for the design of teacher communities seems underdeveloped. Therefore, this study aims to formulate a set of design principles to foster the development of teacher communities in secondary education. The set of design principles is based on a review of literature, as well as on a best-practice case. The case study was used to validate design principles from the literature in the target context. The resulting design principles were based on context-intervention-mechanismoutcome logic that takes into account the context-dependency of interventions as well as the mechanisms that help with understanding of how interventions produce certain outcomes. Implications for practice relate to ownership and co-design of the arrangement. The set of design principles provides a practical basis for teachers and administrators aiming to facilitate community building in their school. Future research is recommended on testing the effectiveness of the arrangement in the target context by means of a multiple case study.NWO-pro

Prevalência e prognóstico dos pacientes com pneumonia associada à ventilação mecânica em um hospital universitário Prevalence of ventilator-associated pneumonia in a university hospital and prognosis for the patients affected

OBJETIVO: Determinar prevalência de pneumonia associada à ventilação mecânica em unidade de terapia intensiva, fatores associados e evolução. MÉTODOS: Foram avaliados 278 pacientes sob ventilação mecânica por mais de 24 horas prospectivamente em hospital universitário. RESULTADOS: Desenvolveram a doença 38,1% dos pacientes, 35,7 casos/1.000 dias de ventilação mecânica: 45,3% por bacilos gram negativos, Pseudomonas aeruginosa (22%) o mais comum e 43,4% por germes multi-resistentes. O grupo com pneumonia associada à ventilação mecânica teve maiores tempos de ventilação mecânica, desmame, permanência no hospital e na unidade de terapia intensiva (p < 0,001); atelectasia, síndrome do desconforto respiratório agudo, pneumotórax, sinusite, traqueobronquite e infecção multirresistente foram mais comuns (p < 0,05). Letalidades na unidade de terapia intensiva e no hospital foram semelhantes. Fatores associados à doença (razão de chances; intervalo de confiança 95%): sinusite aguda (38,8; 3,4 - 441), ventilação mecânica >10 dias (7,7; 4,1 - 14,2), imunodepressão (4,3; 1,3 - 14,3), síndrome do desconforto respiratório agudo (3,5; 1,4 - 9,0), atelectasia (3,0; 1,2 - 7,3), parada cardiorrespiratória (0,18; 0,05 - 0,66) e hemorragia digestiva alta (0,07; 0,009 - 0,62]. Fatores associados ao óbito hospitalar: insuficiência renal crônica (26,1; 1,9 - 350,7), admissão prévia na unidade de terapia intensiva (15,6; 1,6 - 152,0), simplified acute physiologic score II > 50 pontos (11,9; 3,4 - 42,0) e idade > 55 anos (4,4; 1,6 - 12,3). CONCLUSÃO: A pneumonia associada à ventilação mecânica aumentou tempos de ventilação mecânica, permanência na unidade de terapia intensiva e no hospital, número de complicações, mas não a letalidade.<br>OBJECTIVE: To determine the prevalence of ventilator-associated pneumonia in an intensive care unit, as well as to identify related factors and characterize patient evolution. METHODS: This study evaluated 278 patients on mechanical ventilation for more than 24 hours in a university hospital. RESULTS: Ventilator-associated pneumonia developed in 38.1% of the patients, translating to 35.7 cases/1000 ventilator-days: 45.3% were caused by gram-negative agents (Pseudomonas aeruginosa accounting for 22%); and multidrug resistant organisms were identified in 43.4%. In the ventilator-associated pneumonia group, time on mechanical ventilation, time to mechanical ventilation weaning, hospital stays and intensive care unit stays were all longer (p < 0.001). In addition, atelectasis, acute respiratory distress syndrome, pneumothorax, sinusitis, tracheobronchitis and infection with multidrug resistant organisms were more common in the ventilator-associated pneumonia group (p < 0.05). Mortality rates in the intensive care unit were comparable to those observed in the hospital infirmary. Associations between ventilator-associated pneumonia and various factors are expressed as odds ratios and 95% confidence intervals: acute sinusitis (38.8; 3.4-441); > 10 days on mechanical ventilation (7.7; 4.1-14.2); immunosuppression (4.3; 1.3-14.3); acute respiratory distress syndrome (3.5; 1.4-9.0); atelectasis (3.0; 1.2-7.3); cardiac arrest (0.18; 0.05-0.66); and upper gastrointestinal tract bleeding (0.07; 0.009-0.62). The variables found to be associated with in-hospital death were as follows: chronic renal failure (26.1; 1.9-350.7); previous intensive care unit admission (15.6; 1.6-152.0); simplified acute physiologic score II > 50 (11.9; 3.4-42.0); and age > 55 years (4.4; 1.6-12.3). CONCLUSION: Ventilator-associated pneumonia increased the time on mechanical ventilation and the number of complications, as well as the length of intensive care unit and hospital stays, but did not affect mortality rates

Impact of the {omega}-3 to {omega}-6 Polyunsaturated Fatty Acid Ratio on Cytokine Release in Human Alveolar Cells.

BACKGROUND: ω-3 polyunsaturated fatty acids (PUFAs) and ω-6 PUFAs have opposing influences on inflammation. The objective was to determine whether lipopolysaccharide (LPS)-induced cytokine release by human alveolar cells was affected by changes in the ω-3/ω-6 ratio of cell membranes induced by different supplies of PUFAs. METHODS: After LPS challenge, PUFAs were added to alveolar cells as docosahexaenoic acid (DHA, ω-3) and arachidonic acid (AA, ω-6) in 4 different DHA/AA ratios (1:1, 1:2, 1:4, and 1:7), and the effects on cytokine release were measured. RESULTS: The supply of 1:1 and 1:2 DHA/AA ratios reversed the baseline predominance of ω-6 over ω-3 in the ω-3/ω-6 PUFA ratio of cell membranes. The release of proinflammatory cytokines (tumor necrosis factor α, interleukin-6, and interleukin-8) was reduced by 1:1 and 1:2 DHA/AA ratios (P < .01 to P < .001) but increased by 1:4 and 1:7 DHA/AA ratios (P < .01 to P < .001) vs control. The 1:1 and 1:2 ratios increased the release of anti-inflammatory interleukin-10 (P < .001). The balance between proinflammatory and anti-inflammatory cytokines showed an anti-inflammatory response with 1:1 and 1:2 ratios and a proinflammatory response with 1:4 and 1:7 ratios (P < .001). CONCLUSIONS: This study showed that proinflammatory cytokine release was dependent on the proportion of ω-3 in the ω-3/ω-6 ratio of alveolar cell membranes, being reduced with the supply of a high proportion of DHA and increased with a high proportion of AA, respectively. These results support the biochemical basis for current recommendations to shift the PUFA supply from ω-6 to ω-3 in nutrition support of patients with acute lung injury