Do mitochondria use efflux pumps to protect their ribosomes from antibiotics?

Fungal environments are rich in natural and engineered antimicrobials, and this, combined with the fact that fungal genomes are rich in coding sequences for transporters, suggests that fungi are an intriguing group in which to search for evidence of antimicrobial efflux pumps in mitochondria. Herein, the range of protective mechanisms used by fungi against antimicrobials is introduced, and it is hypothesized, based on the susceptibility of mitochondrial and bacterial ribosomes to the same antibiotics, that mitochondria might also contain pumps that efflux antibiotics from these organelles. Preliminary evidence of ethidium bromide efflux is presented and several candidate efflux pumps are identified in fungal mitochondrial proteomes.

Introducing the national COPD resources and outcomes project.

BACKGROUND: We report baseline data on the organisation of COPD care in UK NHS hospitals participating in the National COPD Resources and Outcomes Project (NCROP). METHODS: We undertook an initial survey of participating hospitals in 2007, looking at organisation and performance indicators in relation to general aspects of care, provision of non-invasive ventilation (NIV), pulmonary rehabilitation, early discharge schemes, and oxygen. We compare, where possible, against the national 2003 audit. RESULTS: 100 hospitals participated. These were typically larger sized Units. Many aspects of COPD care had improved since 2003. Areas for further improvement include organisation of acute care, staff training, end-of-life care, organisation of oxygen services and continuation of pulmonary rehabilitation. KEY POINTS: positive change occurs over time and repeated audit seems to deliver some improvement in services. It is necessary to assess interventions such as the Peer Review used in the NCROP to achieve more comprehensive and rapid change.

Psychosocial factors and asthma in a community sample of older adults.

OBJECTIVE: The objective of this study was to investigate the associations between psychosocial factors and asthma in a population-based cohort study of older adults. METHODS: A total of 20,888 participants in the Norfolk cohort of the European Prospective Investigation into Cancer study completed assessments that included details of lifetime self-reported doctor-diagnosed asthma, mood disorder history, social adversity experience, and social support. RESULTS: Doctor-diagnosed asthma was reported by 1699 (8.1%) participants. After adjusting for age, sex, preexisting myocardial infarction, stroke, diabetes, cancer, cigarette smoking, social class, and area deprivation, the psychosocial factors most strongly (and independently) associated with asthma were major depressive disorder (P=.0001), adverse childhood circumstances (P=.005), reported impact of life events experienced in adulthood (P=.003), long-term difficulties in adulthood (P=.04), and negative aspects of confidant support (P=.002). CONCLUSION: These results demonstrate that adverse psychosocial factors cluster among older adults with asthma. These findings may have implications for guiding improvements in asthma management.

Psycho-educational interventions for adults with severe or difficult asthma: a systematic review.

Research highlights psychosocial factors associated with adverse asthma events. This systematic review therefore examined whether psycho-educational interventions improve health and self-management outcomes in adults with severe or difficult asthma. Seventeen controlled studies were included. Characteristics and content of interventions varied even within broad types. Study quality was generally poor and several studies were small. Any positive effects observed from qualitative and quantitative syntheses were mainly short term and, in planned subgroup analyses (involving < 5 trials), effects on hospitalizations, quality of life, and psychological morbidity in patients with severe asthma did not extend to those in whom multiple factors complicate management.

Severity assessment criteria recommended by the British Thoracic Society (BTS) for community-acquired pneumonia (CAP) and older patients. Should SOAR (systolic blood pressure, oxygenation, age and respiratory rate) criteria be used in older people? A compilation study of two prospective cohorts.

OBJECTIVES: To assess the usefulness of the British Thoracic Society guidelines for severity assessment of community-acquired pneumonia (CAP) in predicting mortality and to explore alternative criteria which could be more useful in older patients. DESIGN: Compilation study of two prospective observational cohorts. SETTING AND PARTICIPANTS: A University hospital in Norfolk, UK with a catchment population of 568,000. Subjects were 195 patients (median age = 77 years) who were included in two prospective studies of CAP. MAIN OUTCOME MEASURE: All-cause mortality occurring within the 6 week follow-up. RESULTS: sensitivity, specificity, positive and negative predictive values for study outcome using CURB and CURB-65 were assessed in 189 patients, and CRB-65 in 192 patients out of a total of 195 patients. Our results were comparable with the original study by Lim et al. Although CURB-65 and CRB-65 included age criteria, in effect they did not materially improve the specificity in predicting high-risk patients in both studies. We found that oxygenation measured by ventilation perfusion mismatch (PaO2:FiO2) was the best predictor of outcome in this slightly older cohort [odds ratio (OR) = 0.99 (0.98-0.99), P = 0.0001]. We derived a new set of criteria; SOAR (systolic blood pressure, oxygenation, age and respiratory rate) based on our findings. Their sensitivity, specificity, positive and negative predictive values were 81.0% (58.1-94.6), 59.3% (49.6-68.4), 27.0% (16.6-39.7) and 94.4% (86.2-98.4), respectively, confirming their comparability with existing criteria. CONCLUSIONS: Our Study confirms the usefulness of currently recommended severity rules for CAP in this older cohort. SOAR criteria may be useful as alternative criteria for a better identification of severe CAP in advanced age where both raised urea level above 7 mmol/l and confusion are common.

Clinician-assessed poor compliance identifies adults with severe asthma who are at risk of adverse outcomes.

Our aim was to determine whether clinician-identified poor compliance is useful in identifying, from among adults with severe asthma, patients with characteristics likely to put them at risk of adverse outcomes. Patients with severe asthma (previous hospital admissions and/or prescribed step 4-5 treatment according to British Thoracic Society guidelines) considered by clinicians to be either compliant (C, N = 41) or poorly compliant (PC, N = 92) with aspects of their recommended management (attendance at appointments, taking medication, and monitoring asthma) provided data on symptoms, health service use, medication, self-management practices, physical and psychological comorbidities, and sociodemographic/socioeconomic characteristics. Cross-sectional univariate analyses were used to examine whether the groups differed with respect to self-reported indicators of asthma morbidity and self-management. Logistic regressions were additionally used to explore psychosocial factors independently associated with patients being identified as PC. Compared with C patients, PC patients had significantly poorer self-reported asthma control in terms of medication use, symptoms, time off work, asthma-specific quality of life, primary care visits, emergency attendances, and hospital admissions. This was coupled with poorer self-management practices. Patients identified as PC also had higher levels of physical and psychological comorbidities, were younger, and faced more difficult social and economic circumstances. We identified significant psychological (anxiety) and social (younger age, not working, number of benefits, adverse family circumstances) factors independently associated with patients being identified as PC. Among adults with severe asthma, clinician-assessed poor compliance was useful in distinguishing between two groups that differed significantly in terms of asthma morbidity indicators, self-management practices, and psychosocial characteristics, which have been previously shown to be associated with hospital admissions, near-fatal attacks, and fatal asthma. We conclude that clinician-assessed poor compliance is a useful marker for identifying patients at risk of these adverse outcomes.