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Biomedical subjects

Robert J O Davies

Publications and source records attributed to Robert J O Davies.

At least 19 recordsLinked to original sources
PubMed2006

The bacteriology of pleural infection by genetic and standard methods and its mortality significance.

BACKGROUND: Antibiotic choices for pleural infection are uncertain as its bacteriology is poorly described. METHODS: Pleural fluid from 434 pleural infections underwent standard culture and a screen for bacteria by amplification and sequencing of bacterial 16S ribosomal RNA gene. RESULTS: Approximately 50% of community-acquired infections were streptococcal, and 20% included anaerobic bacteria. Approximately 60% of hospital-acquired infections included bacteria frequently resistant to antibiotics (methicillin-resistant Staphylococcus aureus, 25%; Enterobacteriaceae, 18%; Pseudomonas spp., 5%, enterococci, 12%). Mortality was increased in hospital-acquired infection (hospital, 17/36 [47%]; community, 53/304 [17%]; relative risk, 4.24; 95% confidence interval, 2.07-8.69; p < 0.00001; chi(2), 1 df = 17.47) and in gram-negative (10/22 [45%]), S. aureus (15/34 [44%]), or mixed aerobic infections (13/28 [46%]), compared with streptococcal infection (23/137 [17%]) and infection including anaerobic bacteria (10/49 [20%]; p < 0.00001, chi(2), 4 df = 23.35). CONCLUSION: Pleural infection differs bacteriologically from pneumonia and requires different treatment. Antibiotics for community-acquired infection should treat aerobic and anaerobic bacteria. Hospital-acquired, gram-negative S. aureus and mixed aerobic infections have a high mortality rate.

Adult↗
PubMed2006

The approach to the patient with a parapneumonic effusion.

Parapneumonic effusion is a common clinical problem, and those that go on to develop pleural infection have high morbidity and mortality. The process of pleural infection evolution involves changes in pleural physiology that are increasingly being elucidated and understood. The microbiology of pleural infection has changed over recent years, with clear differences emerging between hospital- and community-acquired infections. Using biochemical surrogates of infection, chest drainage can be undertaken rationally for those who do not respond to antibiotics alone. Recent data suggest that fibrinolytics do not influence outcomes in pleural infection. The optimal type and timing of surgery remain controversial.

Community-Acquired Infections↗
PubMed2006

Diagnosis and management of infectious pleural effusion.

Pleural infection remains a common illness, with a high morbidity and mortality. The development of frank empyema from a simple exudative pleural effusion is a result of biochemical changes within the pleural space in response to bacterial invasion. These changes can be used in the diagnosis of pleural infection and used to predict which patients will require intercostal drainage for resolution of infection. Recent large trials in empyema have further advanced our knowledge of microbiologic patterns, informing important decisions about empiric antibacterial therapy. Diagnosis of pleural infection relies on high clinical suspicion in association with clinical features, radiology, and pleural fluid characteristics. Treatment of pleural infection is based upon accurate and often empiric choice of antibacterial agents, intercostal drainage in certain contexts, and appropriate surgical referral. Intrapleural thrombolytic therapy is not currently recommended for the treatment of pleural infection, on the basis of evidence from the largest randomized trial in empyema to date.

Anti-Bacterial Agents↗
PubMed2005

Needle-track metastases and prophylactic radiotherapy for mesothelioma.

BACKGROUND: Mesothelioma invades the tracts made by chest instrumentation. Prophylactic radiotherapy is effective at preventing malignant seeding at these sites. METHODS: We assessed the use and effectiveness of radiotherapy at our centre in 39 of the 40 patients identified with mesothelioma between January 2000 and September 2003. RESULTS: Thirty-seven (95%) patients received radiotherapy to their chest instrumentation site between 6 and 42 days (median 26 days) following the diagnosis of mesothelioma. The radiotherapy field size varied, from 4 cm square to 14 x 10.5 cm. The radiotherapy was given as 21 Gy in 3 fractions over 1 week. In 3 patients (8%), there was already tumour invasion of the skin at the time of radiotherapy. In 2 other patients (5%), there was tumour recurrence following radiotherapy; in both this was at the edge of the previous radiotherapy fields. Further treatment was administered to an adjacent field in both. One patient with an indwelling pleural catheter developed tumour growth at the catheter insertion site. This was treated successfully with radiotherapy, with no catheter damage. CONCLUSIONS: Prompt radiotherapy referral and radiotherapy field selection is important to maximise the effect of radiotherapy given to prevent chest wall tumour growth. There was no tumour growth in areas that were treated with radiotherapy. Further chest interventions outside the radiotherapy field should be followed with further radiotherapy.

Biopsy, Needle↗
PubMed2005

Pleural effusion: a structured approach to care.

The accumulation of fluid in the pleural space is a common manifestation of a wide range of disease. This review provides a structured approach to the investigation of the patient with a pleural effusion. This should allow an accurate diagnosis to be made with the minimum number of invasive and time-consuming investigations.

Autoimmune Diseases↗
PubMed2005

U.K. Controlled trial of intrapleural streptokinase for pleural infection.

BACKGROUND: Intrapleural fibrinolytic agents are used in the drainage of infected pleural-fluid collections. This use is based on small trials that did not have the statistical power to evaluate accurately important clinical outcomes, including safety. We conducted a trial to clarify the therapeutic role of intrapleural streptokinase. METHODS: In this double-blind trial, 454 patients with pleural infection (defined by the presence of purulent pleural fluid or pleural fluid with a pH below 7.2 with signs of infection or by proven bacterial invasion of the pleural space) were randomly assigned to receive either intrapleural streptokinase (250,000 IU twice daily for three days) or placebo. Patients received antibiotics and underwent chest-tube drainage, surgery, and other treatment as part of routine care. The number of patients in the two groups who had died or needed surgical drainage at three months was compared (the primary end point); secondary end points were the rates of death and of surgery (analyzed separately), the radiographic outcome, and the length of the hospital stay. RESULTS: The groups were well matched at baseline. Among the 427 patients who received streptokinase or placebo, there was no significant difference between the groups in the proportion of patients who died or needed surgery (with streptokinase: 64 of 206 patients [31 percent]; with placebo: 60 of 221 [27 percent]; relative risk, 1.14 [95 percent confidence interval, 0.85 to 1.54; P=0.43), a result that excluded a clinically significant benefit of streptokinase. There was no benefit to streptokinase in terms of mortality, rate of surgery, radiographic outcomes, or length of the hospital stay. Serious adverse events (chest pain, fever, or allergy) were more common with streptokinase (7 percent, vs. 3 percent with placebo; relative risk, 2.49 [95 percent confidence interval, 0.98 to 6.36]; P=0.08). CONCLUSIONS: The intrapleural administration of streptokinase does not improve mortality, the rate of surgery, or the length of the hospital stay among patients with pleural infection.

Anti-Bacterial Agents↗
PubMed2004

CD56bright NK cells are enriched at inflammatory sites and can engage with monocytes in a reciprocal program of activation.

Human NK cells may be divided into a CD56(dim) subset and a CD56(bright) subset. In peripheral blood, CD56(dim) NK cells dominate, whereas in lymph nodes, CD56(bright) NK cells are more common. In this study we show that CD56(bright) NK cells accumulate within inflammatory lesions in a wide variety of clinical diseases affecting several different anatomical sites. We demonstrate that when activated by the monokines IL-12, IL-15, and IL-18, these NK cells promote TNF-alpha production by CD14(+) monocytes in a manner that is dependent on cell:cell contact. Conversely, CD14(+) monocytes synergize with monokines to promote IFN-gamma production by these NK cells. Again, this interaction is dependent on cell:cell contact. The experiments show that CD56(bright) NK cells accumulate in inflammatory lesions and, in the appropriate cytokine environment, can engage with CD14(+) monocytes in a reciprocal activatory fashion, thereby amplifying the inflammatory response. Such a positive feedback loop is likely to be important in the pathogenesis of chronic inflammatory conditions such as rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed2004

Randomized trials describing lung inflammation after pleurodesis with talc of varying particle size.

We report two trials describing whether talc pleurodesis with a mean particle size of less than 15 microm ("mixed" talc) produces more lung and systemic inflammation than tetracycline or "graded" talc (most particles < 10 microm were removed). First, 20 patients with malignant effusions received tetracycline or mixed talc. Changes in lung and systemic inflammation from lung clearance scans, oxygen saturations, and C-reactive protein from baseline to 48 hours after pleurodesis were recorded. Lung inflammation (change in isotope clearance, talc -9.26, SD 14.3 vs. tetracycline 4.10, SD 13.8 minutes; difference = -13.4; 95% confidence interval [CI], -26.6 to -0.2; p = 0.05) and systemic inflammation (change in C-reactive protein, talc 198 SD 79.2 vs. tetracycline 74 SD 79.4 microg/L; difference = 124; 95% CI, 50 to 199; p = 0.004) were greater after talc. Second, 48 patients received mixed or graded talc, and gas exchange was assessed from changes in the alveolar-arterial oxygen gradient. Mixed talc worsened gas exchange (oxygen gradient change, mixed 2.17 SD 1.74 kPa, 16.3 13.1 mm Hg vs. graded 0.72 SD 2.46 kPa 5.4 18.5 mm Hg, difference = 1.45; 95% CI, 0.2 to 2.7; p = 0.03) and induced more systemic inflammation than graded talc. We conclude that the routine use of graded talc for pleurodesis would reduce the morbidity of this procedure.

Blood Gas Analysis↗
PubMed2004

Recent advances in parapneumonic effusion and empyema.

PURPOSE OF REVIEW: Complicated parapneumonic effusion and empyema continue to account for significant morbidity and mortality, and uncertainties remain regarding their optimal management. This review describes recent advances in this field, as well as areas for future research. RECENT FINDINGS: Recent advances have addressed the pathogenesis, bacteriology, and treatment of pleural infection. Key areas for research in the development of empyema include the interplay between inflammatory and coagulation cascades and development of fibrosis within the pleural space. The varied bacteriology of empyema has been more clearly defined, and in particular the differences between community- and hospital-acquired infection highlighted. Studies of treatment have focused particularly on the roles of intrapleural fibrinolytics and surgery. SUMMARY: Increased understanding of the pathogenesis of empyema may ultimately yield novel therapeutic targets. Comprehensive descriptions of the bacteriology of empyema aids antibiotic choice, and the use of intrapleural DNase shows promise in facilitating drainage of infected pleural fluid. Uncertainties remain, such as the role of intrapleural fibrinolytics and the optimal timing of surgical intervention.

Anti-Bacterial Agents↗
PubMed2004

Pleurodesis for malignant pleural effusions: current controversies and variations in practices.

PURPOSE OF REVIEW: Malignant pleural effusions are common, and pleurodesis remains the best method to control re-accumulation of the pleural fluid. There are few randomized controlled trials studying the optimal management of malignant pleural effusions. A recent international survey of pleurodesis practice has highlighted variations in how pleurodesis is performed worldwide. Future research should target these areas of variation to determine the best practice protocols. RECENT FINDINGS: The selection of pleurodesing agents remains controversial. Talc is more effective, but is associated with more adverse effects. Talc pleurodesis is followed by systemic and pulmonary inflammation. This is probably related to systemic embolization of talc following its intrapleural administration, though there are other potential causes that may also play a role. SUMMARY: The practice of pleurodesis varies considerably among individual pulmonologists and among different countries, in most technical aspects. This review serves to highlight some of these variations in practice, as well as reviewing the current literature on pleurodesis practice.

Drainage↗
PubMed2004

The management of pleural space infections.

Pleural infection is responsible for significant morbidity and mortality worldwide, and its clinical management is challenging. The diagnosis of empyema and tuberculous pleurisy may be difficult, and these conditions may be confused with other causes of exudative pleural effusions. Complicated parapneumonic effusion or empyema may present with 'atypical' clinical features; delays in diagnosis are common and may contribute to the high mortality of these infections. Pleural aspiration is the key diagnostic step; pleural fluid that is purulent or that has a pH < 7.2, or organisms on Gram stain or culture, is an indication for formal intercostal drainage. In order to achieve a definitive diagnosis of tuberculous pleurisy, Mycobacterium tuberculosis must be isolated in the culture of pleural fluid, pleural tissue or sputum; demonstration of granulomas in pleural tissue is also suggestive of tuberculosis. The use of pleural fluid biochemical markers, such as adenosine deaminase, in the diagnosis of tuberculous pleurisy varies among clinicians; the diagnostic value of such markers is affected by the background prevalence of tuberculosis and the likelihood of an alternative diagnosis. Uncertainties also remain regarding the treatment of pleural infection. Treatment of complicated parapneumonic effusion and empyema involves prolonged courses of antibiotics and attention to the patient's nutritional state. The role of intrapleural fibrinolytics and the optimal timing of surgical intervention are unknown. The lack of clear predictors of clinical outcome in empyema contributes to the difficulty in treating this condition. The pharmacological treatment of tuberculous pleurisy is the same as for pulmonary tuberculosis; the precise role of steroids in the treatment of tuberculous pleurisy remains uncertain.

Chest Tubes↗
PubMed2004

Diagnostically significant variations in pleural fluid pH in loculated parapneumonic effusions.

STUDY OBJECTIVES: Parapneumonic effusions are common, and measurement of pleural pH is one of the most useful measurements in assessing the need for tube drainage. Use of pleural pH assumes that a single measurement conveys a representative picture of pH throughout the effusion. Often effusions are multiloculated, and varying concentrations of nondiffusible acids such as lactic acid, if present in different concentrations, could mean clinically significant variations in pH between locules. If these differences were large, a single pH measurement could misrepresent the "stage" that the parapneumonic effusion had reached. We therefore set out to test the hypothesis that pH varies significantly between locules in complicated parapneumonic effusions. DESIGN: The study was performed in seven consecutive patients presenting to our institution with complicated parapneumonic effusions. INTERVENTIONS: In each case, pleural pH was measured in several separate pleural fluid locules, using ultrasound-guided pleural fluid sampling. RESULTS: Significant variations were found in pleural fluid visual appearance, pH, and lactate dehydrogenase between locules in four of seven patients. Three of seven patients had variations, resulting in pH levels both above and below 7.2, which is the threshold used in our institution to indicate the need for tube drainage. CONCLUSIONS: This is the first reported series of variation in pleural pH between different locules in complicated parapneumonic effusions. These variations are clinically important and cast light on the mechanisms responsible for the acidosis seen in infected effusions. Physicians should be aware of this when making drainage decisions in these patients using the clinical picture and a single pH result alone.

Adult↗
PubMed2003

A randomized controlled trial of adaptive ventilation for Cheyne-Stokes breathing in heart failure.

Heart failure is associated with Cheyne-Stokes breathing, which fragments patients' sleep. Correction of respiratory disturbance may reduce sleep fragmentation and excessive daytime sleepiness. This randomized prospective parallel trial assesses whether nocturnal-assist servoventilation improves daytime sleepiness compared with the control. A total of 30 subjects (29 male) with Cheyne-Stokes breathing (mean apnea-hypopnea index 19.8 [SD 2.6] and stable symptomatic chronic heart failure (New York Heart Association Class II-IV) were treated with 1 month's therapeutic (n = 15) or subtherapeutic adaptive servoventilation. Daytime sleepiness (Osler test) was measured before and after the trial with change in measured sleepiness the primary endpoint. Secondary endpoints included brain natriuretic peptide levels and catecholamine excretion. Active treatment reduced excessive daytime sleepiness; the mean Osler change was +7.9 minutes (SEM 2.9), when compared with the control, the change was -1.0 minutes (SEM, 1.7), and the difference was 8.9 minutes (95% confidence interval, 1.9-15.9 minutes; p = 0.014, unpaired t test). Significant falls occurred in plasma brain natriuretic peptide and urinary metadrenaline excretion. We conclude that adaptive servoventilation produces an improvement in excessive daytime sleepiness in patients with Cheyne-Stokes breathing and chronic heart failure. This study suggests improvements in neurohormonal activation with this treatment.

Aged↗
PubMed2003

Pleurodesis practice for malignant pleural effusions in five English-speaking countries: survey of pulmonologists.

BACKGROUND: Pleurodesis is important in the management of malignant pleural effusions, but no consensus exists on the optimal agent or methods of pleurodesis. How pleurodesis is practiced worldwide has not been studied. OBJECTIVES: To identify variations in the clinical practice of pleurodesis in major English-speaking countries, and to quantify the experience of pulmonologists on the effectiveness and adverse effects of different pleurodesis agents worldwide. METHODS: Eight hundred fifty-nine pulmonologists practicing in the United States, United Kingdom, Canada, Australia, and New Zealand participated in a Web-based survey. RESULTS: The respondents collectively perform > 8,300 pleurodesis annually. Talc was the preferred agent by most respondents (slurry, 56%; poudrage, 12%), followed by tetracycline derivatives (26%), and bleomycin (7%). Differences were seen in pleurodesis practice patterns among practitioners among and within the surveyed countries. Physicians' overall satisfaction with the available pleurodesis agents was modest (5.0 out of 8), and the reported success rate averaged only 66%. Talc (both poudrage and slurry) was perceived as significantly more effective, but was associated with significantly more pain, nausea, and fever (p < 0.05). Respiratory failure occurred more commonly with talc poudrage than with other agents (p < 0.05), and had been observed by 70% and 54% of physicians who used talc poudrage and slurry, respectively. CONCLUSIONS: Significant variations exist in how pleurodesis is performed worldwide. Pleurodesis agents currently available are perceived as suboptimal. Talc poudrage and slurry were perceived to be more effective, but were associated with more complications, including respiratory failure.

Adult↗
PubMed2002

Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial.

BACKGROUND: Obstructive sleep apnoea is associated with raised blood pressure. If blood pressure can be reduced by nasal continuous positive airway pressure (nCPAP), such treatment could reduce risk of cardiovascular disease in patients with obstructive sleep apnoea. Our aim was to see whether nCPAP for sleep apnoea reduces blood pressure compared with the most robust control intervention subtherapeutic nCPAP. METHODS: We did a randomised parallel trial to compare change in blood pressure in 118 men with obstructive sleep apnoea (Epworth score > 9, and a > 4% oxygen desaturation index of > 10 per h) who were assigned to either therapeutic (n=59) or subtherapeutic (59) nCPAP (about 1 cm H(2)O pressure) for 1 month. The primary outcome was the change in 24-h mean blood pressure. Secondary outcomes were changes in systolic, diastolic, sleep, and wake blood pressure, and relations between blood pressure changes, baseline blood pressure, and severity of sleep apnoea. FINDINGS: Therapeutic nCPAP reduced mean arterial ambulatory blood pressure by 2.5 mm Hg (SE 0.8), whereas subtherapeutic nCPAP increased blood pressure by 0.8 mm Hg (0.7) (difference -3.3 [95% CI -5.3 to -1.3]; p=0.0013, unpaired t test). This benefit was seen in both systolic and diastolic blood pressure, and during both sleep and wake. The benefit was larger in patients with more severe sleep apnoea than those who had less severe apnoea, but was independent of the baseline blood pressure. The benefit was especially large in patients taking drug treatment for blood pressure. INTERPRETATION: In patients with most severe sleep apnoea, nCPAP reduces blood pressure, providing significant vascular risk benefits, and substantially improving excessive daytime sleepiness and quality of life.

Adult↗