An in vitro investigation of the inflammatory response to the strain amplitudes which occur during high frequency oscillation ventilation and conventional mechanical ventilation

The research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College Londo

Non-BBN Constraints On The Key Cosmological Parameters

Since the baryon-to-photon ratio "eta" is in some doubt at present, we ignore the constraints on eta from big bang nucleosynthesis (BBN) and fit the three key cosmological parameters (h, Omega_M, eta) to four other observational constraints: Hubble parameter, age of the universe, cluster gas (baryon) fraction, and effective shape parameter "Gamma". We consider open and flat CDM models and flat "Lambda"-CDM models, testing goodness of fit and drawing confidence regions by the Delta-chi^2 method. CDM models with Omega_M = 1 (SCDM models) are accepted only because we allow a large error on h, permitting h < 0.5. Open CDM models are accepted only for Omega_M \gsim 0.4. Lambda-CDM models give similar results. In all of these models, large eta (\gsim 6) is favored strongly over small eta, supporting reports of low deuterium abundances on some QSO lines of sight, and suggesting that observational determinations of primordial 4He may be contaminated by systematic errors. Only if we drop the crucial Gamma constraint are much lower values of Omega_M and eta permitted.Comment: 12 pages, Kluwer Latex, 2 Postscript figures, to appear in the proceedings of the ISSI Workshop, "The Primordial Nuclei and Their Galactic Evolution" (Bern, May 6-10, 1997), ed. N. Prantzos, M. Tosi, and R. von Steiger (Kluwer, Dordrecht

Participant retention in follow-up studies of prematurely born children

Background: Follow-up studies of infants born prematurely are essential to understand the long-term consequences of preterm birth and the efficacy of interventions delivered in the neonatal period. Retention of participants for follow up studies, however, is challenging, with attrition rates of up to 70%. Our aim was to examine retention rates in two follow-up studies of prematurely born children and identify participant or study characteristics that were associated with higher attrition, and to discuss retention strategies with regard to the literature. Methods: Data from children recruited at birth to one of two studies of prematurely born infants were assessed. The two studies were the United Kingdom Oscillation Study (UKOS, a randomised study comparing two modes of neonatal ventilation in infants born less than 29weeks of gestational age (GA)), and an observational study examining the impact of viral lower respiratory tract infections in infancy in those born less than 36weeks of GA (virus study). The UKOS participants, but not those in the virus study, had regularly been contacted throughout the follow-up period. UKOS subjects were followed up at 11 to 14years of age and subjects in the virus study at 5–7 years of age. At follow up in both studies, pulmonary function and respiratory morbidity were assessed. Retention rates to follow-up in the two studies and baseline characteristics of those who were and were not retained were assessed. Results: Retention was significantly higher in UKOS than the virus study (61% versus 35%, p <0.0001). Subjects lost to UKOS follow up had greater deprivation scores (p <0.001), a greater likelihood of intrauterine tobacco exposure (p =0.001) and were more likely to be of non-white ethnicity (p <0.001). In the virus study, those lost to follow-up had higher birth weights (p =0.036) and were less likely to be oxygen dependent at hospital discharge (p =0.003) or be part of a multiple birth (p =0.048). Conclusions: Higher retention was demonstrated when there was regular contact in the follow-up period. Both social factors and initial illness severity affected the retention into follow-up studies of prematurely born infants, though these factors were not consistent across the two studies.KHP Challenge Fund; National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College Londo

Managing healthcare budgets in times of austerity: the role of program budgeting and marginal analysis

Given limited resources, priority setting or choice making will remain a reality at all levels of publicly funded healthcare across countries for many years to come. The pressures may well be even more acute as the impact of the economic crisis of 2008 continues to play out but, even as economies begin to turn around, resources within healthcare will be limited, thus some form of rationing will be required. Over the last few decades, research on healthcare priority setting has focused on methods of implementation as well as on the development of approaches related to fairness and legitimacy and on more technical aspects of decision making including the use of multi-criteria decision analysis. Recently, research has led to better understanding of evaluating priority setting activity including defining ‘success’ and articulating key elements for high performance. This body of research, however, often goes untapped by those charged with making challenging decisions and as such, in line with prevailing public sector incentives, decisions are often reliant on historical allocation patterns and/or political negotiation. These archaic and ineffective approaches not only lead to poor decisions in terms of value for money but further do not reflect basic ethical conditions that can lead to fairness in the decision-making process. The purpose of this paper is to outline a comprehensive approach to priority setting and resource allocation that has been used in different contexts across countries. This will provide decision makers with a single point of access for a basic understanding of relevant tools when faced with having to make difficult decisions about what healthcare services to fund and what not to fund. The paper also addresses several key issues related to priority setting including how health technology assessments can be used, how performance can be improved at a practical level, and what ongoing resource management practice should look like. In terms of future research, one of the most important areas of priority setting that needs further attention is how best to engage public members

Cost-Effectiveness Analysis of Stereotactic Ablative Body Radiation Therapy Compared With Surgery and Radiofrequency Ablation in Two Patient Cohorts: Metastatic Liver Cancer and Hepatocellular Carcinoma

Aims: To compare the cost-effectiveness of stereotactic ablative body radiation therapy (SABR) with radiofrequency ablation and surgery in adult patients with metastatic liver cancer and hepatocellular carcinoma (HCC). / Materials and methods: Two patient cohorts were assessed: liver oligometastases and HCC. For each patient cohort, a decision analytic model was constructed to assess the cost-effectiveness of interventions over a 5-year horizon. A Markov process was embedded in the decision model to simulate the possible prognosis of cancer. Data on transition probabilities, survival, side-effects, quality of life and costs were obtained from published sources and the SABR Commissioning through Evaluation (CtE) scheme. The primary outcome was the incremental cost-effectiveness ratio with respect to quality-adjusted life-years. The robustness of the results was examined in a sensitivity analysis. Analyses were conducted from a National Health Service and Personal Social Services perspective. / Results: In the base case analysis, which assumed that all three interventions were associated with the same cancer progression rates and mortality rates, SABR was the most cost-effective intervention for both patient cohorts. This conclusion was sensitive to the cancer progression rate, mortality rate and cost of interventions. Assuming a willingness-to-pay threshold of £20 000 per quality-adjusted life-year, the probability that SABR is cost-effective was 57% and 50% in liver oligometastases and HCC, respectively. / Conclusions: Our results indicate a potential for SABR to be cost-effective for patients with liver oligometastases and HCC. This finding supports further investigation in clinical trials directly comparing SABR with surgery and radiofrequency ablation

Outdoor air pollution and respiratory health in patients with COPD

Cannot archive published pdf, only submitted/accepted version of the article. Full version published by BMJ Publishing Group Ltd (& BTS) under licence. First published by Thorax Online, on April 1, 2011. Doi:10.1136/thx.2010.155358

Clinical characteristics of emergency department heart failure patients initially diagnosed as non-heart failure

BACKGROUND: Since previous studies suggest the emergency department (ED) misdiagnosis rate of heart failure is 10–20% we sought to describe the characteristics of ED patients misdiagnosed as non-decompensated heart failure in the ED. METHODS: We analyzed a prospective convenience sample of 439 patients at 4 emergency departments who presented with signs or symptoms of decompensated heart failure. Patients with a cardiology criterion standard diagnosis of decompensated heart failure and an ED diagnosis of decompensated heart failure were compared to patients with a criterion standard of decompensated heart failure but no ED diagnosis of decompensated heart failure. Two senior cardiology fellows retrospectively determined the patient's heart failure status during their acute ED presentation. The Mann-Whitney u-test for two groups, the Kruskall-Wallis test for multiple groups, or Chi-square tests, were used as appropriate. RESULTS: There were 173 (39.4%) patients with a criterion standard diagnosis of decompensated heart failure. Among those with this criterion standard diagnosis of decompensated heart failure, discordant patients without an ED diagnosis of decompensated heart failure (n = 58) were more likely to have a history of COPD (p = 0.017), less likely to have a previous history of heart failure (p = 0.014), and less likely to have an elevated b-type natriuretic peptide (BNP) level (median 518 vs 764 pg/ml; p = 0.038) than those who were given a concordant ED diagnosis of decompensated heart failure. BNP levels were higher in those with a criterion standard diagnosis of decompensated heart failure than in those without a criterion standard diagnosis (median 657 vs 62.7 pg/ml). However, 34.6% of patients with decompensated heart failure had BNP levels in the normal (<100 pg/ml; 6.1%) or indeterminate range (100–500 pg/ml; 28.5%). CONCLUSION: We found the ED diagnoses of decompensated heart failure to be discordant with the criterion standard in 14.3% of patients, the vast majority of which were due to a failure to diagnose heart failure when it was present. Patients with a previous history of COPD, without a previous history of heart failure and with lower BNP levels were more likely to have an ED misdiagnosis of non-decompensated heart failure. Readily available, accurate, objective ED tests are needed to improve the early diagnosis of decompensated heart failure in ED patients

Postnatal dexamethasone, respiratory and neurodevelopmental outcomes at two years in babies born extremely preterm.

IMPORTANCE: Postnatal dexamethasone is associated with reduction in bronchopulmonary dysplasia. There remains, however, concern that its short-term benefits are accompanied by long-term adverse effects e.g. poorer neurodevelopmental outcomes. OBJECTIVE: Our aim was to determine the effects of administration of postnatal dexamethasone on respiratory and neurodevelopmental outcome at two years of age after adjusting for neonatal and infant risk factors. MATERIALS AND METHODS: The study included 412 infants born at 23-28 weeks of gestation, 29% had received postnatal dexamethasone. Two outcomes were examined, respiratory hospital admissions in the past 12 months and neurodevelopmental impairment. Logistic regression, adjusted for sex, birthweight z-score, gestation, maternal smoking, oxygen dependency at 36 weeks, airleak, patent ductus arteriosus, pulmonary haemorrhage, major ultrasound abnormality, mode of ventilation and age at assessment, was undertaken. RESULTS: After adjustment, postnatal dexamethasone was associated with significantly increased proportions of both respiratory hospital readmission: (0.35 vs 0.15, difference = 0.20; 95% CI: 0.08, 0.31) and neurodevelopmental impairment (0.59 vs 0.45, difference = 0.14; 95% CI: 0.02, 0.26). CONCLUSIONS: Postnatal dexamethasone use in extremely preterm infants is associated with increased risks of respiratory hospital admissions and neurodevelopmental impairment. These associations were not explained by excess neonatal morbidities

Effect of dexamethasone exposure on the neonatal unit on the school age lung function of children born very prematurely

The objective of this study was to determine the impact of postnatal dexamethasone treatment on the neonatal unit on the school age lung function of very prematurely born children. Children born prior to 29 weeks of gestational age had been entered into a randomised trial of two methods of neonatal ventilation (United Kingdom Oscillation Study). They had comprehensive lung function measurements at 11 to 14 years of age. One hundred and seventy-nine children born at a mean gestational age of 26.9 (range 23–28) weeks were assessed at 11 to 14 years; 50 had received postnatal dexamethasone. Forced expiratory flow at 75% (FEF75), 50%, 25% and 25–75% of the expired vital capacity, forced expiratory volume in one second, peak expiratory flow and forced vital capacity and lung volumes including total lung capacity and residual volume were assessed. Lung function outcomes were compared between children who had and had not been exposed to dexamethasone after adjustment for neonatal factors using linear mixed effects regression. After adjustment for confounders all the mean spirometry results were between 0.38 and 0.87 standard deviations lower in those exposed to dexamethasone compared to the unexposed. For example, the mean FEF75z-score was 0.53 lower (95% CI 0.21 to 0.85). The mean lung function was lower as the number of courses of dexamethasone increased. In conclusion, postnatal dexamethasone exposure was associated with lower mean lung function at school age in children born extremely prematurely. Our results suggest the larger the cumulative dose the greater the adverse effect on lung function at follow-up