Devitalized Saos-2, cultured human osteosarcoma cells, or guanidinium-hydrochloride (GuHCl) extracts of these cells, induce ectopic bone and marrow formation when implanted subcutaneously in Nu/Nu mice. The aim of the present study was to characterize the bone marrow induced by Saos-2 cell extracts, specifically to determine which of the four major hematopoietic cell lineages: erythropoietic, granulopoietic, lymphopoietic and megakaryocytic, are induced by Saos-2 cell derivatives. Methods: Immunohistochemical localization of specific antigens was used to determine the presence of each major cell type (glycophorin A for erythropoietic, neutrophil elastase for granulopoietic, factor-VIII related antigen for megakaryocytes, and CD79a for B lymphocytes). Results: Standard H & E stains confirmed the presence of normally organized apparently complete bone marrow within all newly induced bone at 3 weeks post-implantation of devitalized Saos-2 cells. Immunohistochemistry confirmed the presence of erythropoietic cells, granulopoietic cells, megakaryocytes and B lymphocytes in the ectopic marrow. Conclusion: Saos-2 cells (freeze-dried) or their extracts, implanted subcutaneously into Nu/Nu mice, can induce normal marrow that is host-derived, and contains all major hematopoietic cell lineages. Clinical Significance: Saos-2 induced marrow could potentially restore deficient marrow and promote bone repair.
Bone marrow induction; bone tumors; hematopoiesis; lineage-specific biomarkers; osteosarcoma
Measurement of hospital quality has traditionally focused on processes of care and post-procedure outcomes. Appropriateness measures for percutaneous coronary intervention (PCI) assess quality as it relates to patient selection in the context of anticipated benefits relative to potential harm. The association, if any, between patient selection for PCI and processes of care and post-procedural outcomes is unknown. Defining whether these measures are redundant or complementary can inform the optimal range of metrics for monitoring quality.
We included patients undergoing non-acute (elective) PCI within the NCDR CathPCI Registry® between July 2009 and April 2011. We examined the association between a hospital’s proportion of non-acute PCIs categorized as inappropriate by the 2009 Appropriate Use Criteria (AUC) for Coronary Revascularization and in-hospital mortality, bleeding complications, and use of optimal guideline-directed medical therapy at discharge (i.e. aspirin, thienopyridines, and statins).
A total of 203,531 non-acute PCIs from 779 hospitals were classified by the AUC. Of these, 101,779 (50.0%) were classified as appropriate, 77,220 (35.5%) as uncertain, and 24,532 (12.1%) as inappropriate. When categorized as hospital tertiles, the range of inappropriate PCI was 0.0 to 8.1% in the lowest-tertile, 8.1 to 15.2% in the middle-tertile, and 15.2 to 58.6% in the highest-tertile. Compared with lowest-tertile hospitals, mortality was not significantly different at middle-tertile (adjusted odds ratio [OR] 0.93; 95% confidence interval [CI] 0.73 to 1.19) or highest-tertile hospitals (OR 1.12; 95% CI 0.88 to 1.43; p=0.35 for differences between any tertile). Similarly, risk-adjusted bleeding did not vary significantly (middle-tertile OR 1.13; 95% CI 1.02 to 1.16; highest-tertile OR 1.02; 95% CI 0.91 to 1.16; p=0.07 for differences between any tertile) nor did use of optimal therapy at discharge after PCI (85.3% vs. 85.7% vs. 85.2%; P=0.58).
In a national cohort of non-acute PCIs, a hospital’s proportion of inappropriate PCIs was not associated with in-hospital mortality, bleeding, or medical therapy at discharge. These findings suggest that PCI appropriateness measures aspects of hospital PCI quality that are independent of, and complementary to, traditional quality metrics.
Appropriateness criteria; Coronary artery disease; Percutaneous coronary intervention; Utilization; Hospital; Quality of care; Health services research
Background: Short-term exposure to ozone has been associated with increased daily mortality. The shape of the concentration–response relationship—and, in particular, if there is a threshold—is critical for estimating public health impacts.
Objective: We investigated the concentration–response relationship between daily ozone and mortality in five urban and five rural areas in the United Kingdom from 1993 to 2006.
Methods: We used Poisson regression, controlling for seasonality, temperature, and influenza, to investigate associations between daily maximum 8-hr ozone and daily all-cause mortality, assuming linear, linear-threshold, and spline models for all-year and season-specific periods. We examined sensitivity to adjustment for particles (urban areas only) and alternative temperature metrics.
Results: In all-year analyses, we found clear evidence for a threshold in the concentration–response relationship between ozone and all-cause mortality in London at 65 µg/m3 [95% confidence interval (CI): 58, 83] but little evidence of a threshold in other urban or rural areas. Combined linear effect estimates for all-cause mortality were comparable for urban and rural areas: 0.48% (95% CI: 0.35, 0.60) and 0.58% (95% CI: 0.36, 0.81) per 10-µg/m3 increase in ozone concentrations, respectively. Seasonal analyses suggested thresholds in both urban and rural areas for effects of ozone during summer months.
Conclusions: Our results suggest that health impacts should be estimated across the whole ambient range of ozone using both threshold and nonthreshold models, and models stratified by season. Evidence of a threshold effect in London but not in other study areas requires further investigation. The public health impacts of exposure to ozone in rural areas should not be overlooked.
concentration–response function; daily mortality; ozone; U.K. population
Background: The effect of ambient air pollution on global variations and trends in asthma prevalence is unclear.
Objectives: Our goal was to investigate community-level associations between asthma prevalence data from the International Study of Asthma and Allergies in Childhood (ISAAC) and satellite-based estimates of particulate matter with aerodynamic diameter < 2.5 µm (PM2.5) and nitrogen dioxide (NO2), and modelled estimates of ozone.
Methods: We assigned satellite-based estimates of PM2.5 and NO2 at a spatial resolution of 0.1° × 0.1° and modeled estimates of ozone at a resolution of 1° × 1° to 183 ISAAC centers. We used center-level prevalence of severe asthma as the outcome and multilevel models to adjust for gross national income (GNI) and center- and country-level sex, climate, and population density. We examined associations (adjusting for GNI) between air pollution and asthma prevalence over time in centers with data from ISAAC Phase One (mid-1900s) and Phase Three (2001–2003).
Results: For the 13- to 14-year age group (128 centers in 28 countries), the estimated average within-country change in center-level asthma prevalence per 100 children per 10% increase in center-level PM2.5 and NO2 was –0.043 [95% confidence interval (CI): –0.139, 0.053] and 0.017 (95% CI: –0.030, 0.064) respectively. For ozone the estimated change in prevalence per parts per billion by volume was –0.116 (95% CI: –0.234, 0.001). Equivalent results for the 6- to 7-year age group (83 centers in 20 countries), though slightly different, were not significantly positive. For the 13- to 14-year age group, change in center-level asthma prevalence over time per 100 children per 10% increase in PM2.5 from Phase One to Phase Three was –0.139 (95% CI: –0.347, 0.068). The corresponding association with ozone (per ppbV) was –0.171 (95% CI: –0.275, –0.067).
Conclusion: In contrast to reports from within-community studies of individuals exposed to traffic pollution, we did not find evidence of a positive association between ambient air pollution and asthma prevalence as measured at the community level.
air pollution; asthma prevalence; children; epidemiology; global; nitrogen dioxide; ozone; particulate matter; satellite observations
The development of disease-modifying pharmacologic therapy for osteoarthritis (OA) currently faces major obstacles, largely because the regulatory mechanisms for the function of adult articular chondrocytes remain unclear. We previously demonstrated that lack of Nfat1, one of the NFAT (nuclear factor of activated T cells) transcription factors, causes OA-like changes in adult mice. This study aimed to identify whether Nfat1 specifically regulates adult articular chondrocyte function and its age-dependent regulatory mechanism using both Nfat1-deficient and wild-type mice. Deletion of Nfat1 did not induce OA-like articular chondrocyte dysfunction (e.g., overexpression of proinflammatory cytokines and matrixdegrading proteinases) until the adult stage. RNAi-mediated Nfat1 knockdown caused dysfunction of wild-type adult articular chondrocytes. Nfat1 expression in wild-type articular chondrocytes was low in the embryonic, but high in the adult stage. Chromatin immunoprecipitation assays demonstrated that an increase in Nfat1 expression in articular chondrocytes was associated with increased H3K4me2 (a histone modification linked to transcriptional activation); while a decrease in Nfat1 expression in articular chondrocytes was correlated with increased H3K9me2 (a histone modification linked to transcriptional repression). Knockdown of lysine-specific demethylase-1 (Lsd1) in embryonic articular chondrocytes up-regulated Nfat1 expression concomitant with increased H3K4me2 at the Nfat1 promoter. Knockdown of Jmjc-containing histone demethylase-2a (Jhdm2a) in 6-month articular chondrocytes down-regulated Nfat1 expression concomitant with increased H3K9me2 at the Nfat1 promoter. These results suggest that Nfat1 is an essential transcriptional regulator of chondrocyte homeostasis in adult articular cartilage. Age-dependent Nfat1 expression in articular chondrocytes is regulated by dynamic histone methylation, one of the epigenetic mechanisms that regulate gene transcription.
Articular chondrocyte; Nfat1; gene expression; histone modifications; epigenetics
Objective. To compare the reliability and credibility of Angoff-based, absolute criteria derived by faculty, alumni, and a combination of alumni and faculty judge panels.
Methods. Independently, faculty, alumni, and mixed faculty-alumni judge panels developed pass/fail criteria for an 86-item test. Generalizability and decision studies were performed. Root mean square errors (RMSE) and 95% confidence intervals were calculated for reliability and credibility assessment. School graduate performance upon the North American Licensure Examination (NAPLEX) was the comparator for credibility assessment.
Results. RMSEs were 1.06%, 1.42%, and 2.32% for the alumni, faculty, and mixed judge panels respectively. The school's NAPLEX pass rate was 97.5%. This rate triangulated well with the faculty judge panel (pass rate = 93.9%, CI95% = 87.1% - 98.2%), but did not with either mixed judge or alumni judge panels.
Conclusions. Faculty-derived criteria offer superior pass/fail decision defensibility relative to both alumni derived and mixed faculty-alumni derived criteria.
Background: Current air quality standards for particulate matter (PM) use the PM mass concentration [PM with aerodynamic diameters ≤ 10 μm (PM10) or ≤ 2.5 μm (PM2.5)] as a metric. It has been suggested that particles from combustion sources are more relevant to human health than are particles from other sources, but the impact of policies directed at reducing PM from combustion processes is usually relatively small when effects are estimated for a reduction in the total mass concentration.
Objectives: We evaluated the value of black carbon particles (BCP) as an additional indicator in air quality management.
Methods: We performed a systematic review and meta-analysis of health effects of BCP compared with PM mass based on data from time-series studies and cohort studies that measured both exposures. We compared the potential health benefits of a hypothetical traffic abatement measure, using near-roadway concentration increments of BCP and PM2.5 based on data from prior studies.
Results: Estimated health effects of a 1-μg/m3 increase in exposure were greater for BCP than for PM10 or PM2.5, but estimated effects of an interquartile range increase were similar. Two-pollutant models in time-series studies suggested that the effect of BCP was more robust than the effect of PM mass. The estimated increase in life expectancy associated with a hypothetical traffic abatement measure was four to nine times higher when expressed in BCP compared with an equivalent change in PM2.5 mass.
Conclusion: BCP is a valuable additional air quality indicator to evaluate the health risks of air quality dominated by primary combustion particles.
air quality management; black carbon; combustion particles; health effects; particulate matter; review
Acute anterior myocardial infarctions caused by proximal left anterior descending (LAD) artery occlusions are associated with a higher morbidity and mortality. Early identification of high-risk patients via the 12-lead electrocardiogram (ECG) could assist physicians and emergency response teams in providing early and aggressive care for patients with anterior ST-elevation myocardial infarctions (STEMI). Approximately 25% of US hospitals have primary percutaneous coronary intervention (PCI) capability for the treatment of acute myocardial infarctions. Given the paucity of hospitals capable of PCI, early identification of more severe myocardial infarction may prompt emergency medical service routing of these patients to PCI-capable hospitals. We sought to determine if the 12 lead ECG is capable of predicting proximal LAD artery occlusions.
In a retrospective, post-hoc analysis of the Pre-Hospital Administration of Thrombolytic Therapy with Urgent Culprit Artery Revascularization pilot trial, we compared the ECG findings of proximal and nonproximal LAD occlusions for patients who had undergone an ECG within 180 minutes of symptom onset.
In this study, 72 patients had anterior STEMIs, with ECGs performed within 180 minutes of symptom onset. In patients who had undergone ECGs within 60 minutes (n = 35), the mean sum of ST elevation (STE) in leads V1 through V6 plus ST depression (STD) in leads II, III, and aVF was 19.2 mm for proximal LAD occlusions and 11.7 mm for nonproximal LAD occlusions (P = 0.007). A sum STE in V1 through V6 plus STD in II, III, and aVF of at least 17.5 mm had a sensitivity of 52.3%, specificity of 92.9%, positive predictive value of 91.7%, and negative predictive value of 56.5% for proximal LAD occlusions. When the ECG was performed more than 60 minutes after symptom onset (n = 37), there was no significant difference in ST-segment deviation between the 2 groups.
The sum STE (V1-V6) and STD (II, III, aVF) on a 12-lead ECG can be used to predict proximal LAD occlusions if performed within the first hour of symptom onset. This should be considered a high-risk finding and may prompt prehospital direction of such patients to PCI-capable hospitals.
One of the major problems faced in the analysis of the human serum proteome is the broad dynamic range of its protein constituents. High abundance proteins, such as human serum albumin (HSA) and gamma-immunoglobulin (IgG), which together comprise 75% of total serum protein content, inhibit the analysis of lower abundant proteins of interest. Affinity-based depletion strategies are often employed to selectively remove these high abundance proteins in order to enrich the lower abundant proteins and facilitate their analysis. Traditionally, antibody-based schemes are used to produce affinity-binding ligands for HSA and IgG. Variability in the production of these antibodies leads to a wide variety of specificities and selectivities. Thus, the efficiencies for antibody-based depletion strategies for the selective removal of high abundance proteins in human serum can vary broadly, from 70 to 95%, and can dramatically affect the reproducibility of human serum proteome studies. Here, a new approach to affinity-based serum albumin removal is presented. Instead of utilizing a traditional antibody based depletion approach, the ProteaPrep albumin depletion capture ligand is a recombinant bacterial protein that is highly purified for robust, efficient removal of albumin from human serum samples. The recombinant ligand technology produces binding constants with human serum albumin (Kd ∼ 1 × 10–11M) that are significantly stronger than antibody-based methods, which have binding constants that range from Kd's of 1 × 10-6 to 1 ×10-8 M. The results show that the functionalized beads bind and remove albumin from serum in a highly efficient and rapid manner. Depletion efficiencies are 99% for the selective removal of HSA from serum samples in less than 20 minutes. The recombinant bacterial protein ligands are shown to be effective for the depletion of albumin from the sera of other species, including mouse, rat, pig, horse, cow, and monkey.
Trends in asthma indicators from population surveys (prevalence) and routine statistics (primary care, prescriptions, hospital admissions and mortality) in the UK were reviewed from 1955 to 2004. The prevalence of asthma increased in children by 2 to 3‐fold, but may have flattened or even fallen recently. Current trends in adult prevalence are flat. The prevalence of a life‐time diagnosis of asthma increased in all age groups. The incidence of new asthma episodes presenting to general practitioners increased in all ages to a plateau in the mid 1990s and has declined since. During the 1990s, the annual prevalence of new cases of asthma and of treated asthma in general practice showed no major change. Hospital admissions increased from the early 1960s, more so in children, until the late 1980s and have fallen since. Asthma mortality showed two waves, a shorter and more intense one in the mid 1960s and a longer and less intense one in the late 1970s and early 1980s. The relative roles of diagnostic transfer, coding changes, medical care and epidemiological factors are discussed.
Allergic disorders are common in the UK. This study reviews recent UK time trends in the prevalence, morbidity and mortality for allergic disorders, excluding asthma.
A trend analysis was performed over recent decades of national, representative or repeat surveys, primary care consultations, prescriptions, hospital admissions, and mortality.
Serial surveys showed that the prevalence of diagnosed allergic rhinitis and eczema in children have both trebled over the last three decades. While these long term trends were paralleled by the prevalence of disease symptoms, more recent symptom prevalence data suggest a decline. Similarly, GP consultation rates rose by 260% for hay fever and by 150% for eczema overall during the period 1971–91, but rates have stabilised over the past decade. Hospital admissions for eczema have been stable since 1995, and hospital admissions for allergic rhinitis have fallen to about 40% of their 1990 levels. Since 1990, admissions for anaphylaxis have increased by 700%, for food allergy by 500%, for urticaria by 100%, and for angio‐oedema by 40%. Prescriptions issued for all types of allergy have increased since 1991.
The prevalence and healthcare usage for eczema and hay fever have increased substantially over recent decades, but may now be stabilising or even falling. In contrast, admissions for some systemic allergic diseases have risen sharply in the last decade which may indicate a rising incidence of these conditions. Although changes in treatment and other healthcare factors may have contributed to these trends, there may also be a change in the aetiology of allergic disease in the UK.
trend; allergic disease; epidemiology
To describe the control and management of a syphilis outbreak in female street sex workers (SSWs) in east London.
Following the identification of several cases of infectious syphilis in SSWs in east London, a targeted service for screening and treatment of syphilis and other sexually transmitted infections was developed. A multidisciplinary team (MDT) joined an existing outreach service to facilitate this. Once it became apparent that this was not an isolated case, an outbreak control team (OCT) was established.
Between April and December 2004 a total of 14 (58%) women with 15 cases of infectious syphilis were identified in 24 SSWs: 14/15 (93%) received treatment. Epidemiological treatment for syphilis was also given to the rest of SSWs at the initial visit. Several coexistent STIs were identified in this cohort. As part of the enhanced outbreak surveillance in north east London, 21 cases of infectious syphilis were reported in SSWs between April 2004 and December 2005.
Outbreak management in this population was challenging: an MDT approach was crucial in identifying and treating syphilis to prevent onward transmission. There was a high prevalence of syphilis and other STIs in this cohort, and we treated the majority of cases. The formation of an OCT enabled us to monitor the outbreak and implement control measures more effectively. The novel intervention we describe has proved valuable in helping to control this syphilis outbreak.
street sex workers; syphilis; outreach
Associations between traffic pollution on the street of residence and a range of respiratory and allergic outcomes in children have been reported in developed countries, but little is known about such associations in developing countries.
The third phase of the International Study of Asthma and Allergies in Childhood (ISAAC) was carried out in 13- to 14-year-old and 6- to 7-year-old children across the world. A question about frequency of truck traffic on the street of residence was included in an additional questionnaire. We investigated the association between self-reported truck traffic on the street of residence and symptoms of asthma, rhinoconjunctivitis, and eczema with logistic regression. Adjustments were made for sex, region of the world, language, gross national income, and 10 other subject-specific covariates.
Frequency of truck traffic on the street of residence was positively associated with the prevalence of symptoms of asthma, rhinoconjunctivitis, and eczema with an exposure–response relationship. Odds ratios (95% confidence intervals) for “current wheeze” and “almost the whole day” versus “never” truck traffic were 1.35 (1.23–1.49) for 13- to 14-year-olds and 1.35 (1.22–1.48) for 6- to 7-year-olds.
Higher exposure to self-reported truck traffic on the street of residence is associated with increased reports of symptoms of asthma, rhinitis, and eczema in many locations in the world. These findings require further investigation in view of increasing exposure of the world’s children to traffic.
air pollution; asthma; eczema; rhinitis; truck traffic
Outdoor aeroallergens are one of a number of environmental factors thought to precipitate asthma exacerbations.
To investigate the short term associations between daily fungal spore concentrations and indicators of daily asthma exacerbations in a large urban population.
Daily counts of visits for asthma to family physicians and hospital accident and emergency (A&E) departments and emergency hospital admissions in London 1992–93 were compiled. Daily concentrations of fungal spores (30 species), daily average temperature, humidity, and concentrations of pollen and outdoor air pollution were also compiled. The analysis was restricted to the period when fungal spores were most prevalent (June to mid October). Non‐parametric regression time series methods were used to assess associations controlling for seasonality, day of week, and meteorological factors. The sensitivity of the findings to the inclusion of pollen and air pollution into the models was also assessed.
In children aged 0–14 years the relative risks for increases in the number of A&E visits and hospital admissions associated with changes in fungal spore concentrations from the lower to upper quartiles were 1.06 (95% CI 0.94 to 1.18) and 1.07 (0.97 to 1.19) respectively. The addition of pollen or air pollutants had little impact on the observed associations. A number of individual spore taxa, in particular Alternaria, Epicoccum, Agrocybe, Mildews, and both coloured and colourless Basidiospores and Ascospores, were associated with increases in the number of emergency visits and hospital admissions for asthma, although the precision of these estimates were low. No evidence was found for associations in adults.
Fungal spore concentrations may provoke or exacerbate asthma attacks in children resulting in visits to A&E departments and emergency hospital admissions. These findings were unlikely to be due to confounding by other environmental factors. The associations were comparable to those observed for ambient air pollution from similarly designed studies.
aeroallergens; asthma exacerbations; time series
Hospital admission rates for asthma in Britain rose during the 1980s and fell during the 1990s, but less is known about recent trends in the prevalence of asthma.
In 1991 and 2002 the same questionnaire was distributed to parents of all school pupils in year 3 (aged 7–8 years) in the London borough of Croydon. Parents of currently wheezy children were then invited for home interview (100% targeted in 1991, 66% in 2002).
The prevalence of wheeze during the previous year increased from 12.9% in 1991 to 17.8% in 2002 (prevalence ratio 1.39 (95% CI 1.23 to 1.56)). Increases were observed in frequent (1.54 (95% CI 1.16 to 2.03)) and infrequent attacks, severe speech limiting episodes (2.25 (95% CI 1.34 to 3.77)), and night waking (1.36 (95% CI 1.07 to 1.72)), and in the reported use of steroids (19.9% v 64.1% of currently wheezy children). Nevertheless, the proportions reporting a visit to the GP at his/her surgery for wheeze in the previous year (prevalence ratio 1.15 (95% CI 0.91 to 1.45)) or an outpatient visit (0.98 (95% CI 0.49 to 1.94)) changed little and an increase in reported casualty attendance (1.66 (95% CI 0.89 to 3.07)) was non‐significant.
There is evidence of an increase in the prevalence of asthma among British primary school children between 1991 and 2002. The absence of a corresponding increase in health service utilisation data may reflect more widespread prophylactic treatment and/or changes in the use and provision of medical services.
asthma; prevalence; children; medical services
Background: Studies have linked asthma death to either increased or decreased use of medical services.
Methods: A population based case-control study of asthma deaths in 1994–8 was performed in 22 English, six Scottish, and five Welsh health authorities/boards. All 681 subjects who died were under the age of 65 years with asthma in Part I on the death certificates. After exclusions, 532 hospital controls were matched to 532 cases for age, district, and date of asthma admission/death. Data were extracted blind from primary care records.
Results: The median age of the subjects who died was 53 years; 60% of cases and 64% of controls were female. There was little difference in outpatient attendance (55% and 55%), hospital admission for asthma (51% and 54%), and median inpatient days (20 days and 15 days) in the previous 5 years. After mutual adjustment and adjustment for sex, using conditional logistic regression, three variables were independently associated with asthma death: fewer general practice contacts (odds ratio 0.82 (95% confidence interval (CI) 0.74 to 0.91) per 5 contacts) in the previous year, more home visits (1.14 (95% CI 1.08 to 1.21) per visit) in the previous year, and fewer peak expiratory flow recordings (0.83 (95% CI 0.74 to 0.92) per occasion) in the previous 3 months. These associations were similar after adjustment for markers of severity, psychosocial factors, systemic steroids, short acting bronchodilators and antibiotics, although the association with peak flow was weakened and just lost significance.
Conclusion: Asthma death is associated with less use of primary care services. Both practice and patient factors may be involved and a better understanding of these may offer possibilities for reducing asthma death.
To determine the efficacy and tolerability of SPI-77 (sterically stabilised liposomal cisplatin) at three dose levels in patients with advanced non-small-cell lung cancer (NSCLC). Patients had Stage IIIB or IV NSCLC and were chemo-naïve, and Eastern Oncology Cooperative Group 0–2. The first cohort received SPI-77 at 100 mg m−2, the second 200 mg m−2 and the final cohort 260 mg m−2. Patients had also pharmacokinetics and analysis of leucocyte platinum (Pt)-DNA adducts performed. Twenty-six patients were treated, with 22 patients being evaluable for response. Only one response occurred at the 200 mg m−2 dose level for an overall response rate of 4.5% (7.1% at ⩾200 mg m−2). No significant toxicity was noted including nephrotoxicity or ototoxicity aside from two patients with Grade 3 nausea. No routine antiemetics or hydration was used. The pharmacokinetic profile of SPI-77 was typical for a liposomally formulated drug, and the AUC appeared to be proportional to the dose of SPI-77. Plasma Pt levels and leucocyte DNA adduct levels did not appear to rise with successive doses. SPI-77 demonstrates only modest activity in patients with NSCLC.
NSCLC; SPI-77; liposomes; cisplatin
Background: Little information exists on injury and factors associated with injury in working youth aged 10–14 years. Most studies do not involve children younger than 15.
Methods: A cross-sectional anonymous survey was administered to middle school students in five school districts and one large urban school in October 2001.
Results: Of the 3189 working middle school students who responded to the survey, the majority were employed in informal job settings, such as working for someone in a home, newspaper delivery, and working on family farms or in family businesses. Overall, 18% of children reported being injured at work. Of those injured, 26% reported that their injury was severe enough to affect their activities for more than three days. Variables that were associated with injury included having a "near-miss" incident at work (AOR 6.61, 95% CI 4.92 to 8.89), having a co-worker injured (AOR 2.65, 95% CI 1.95 to 3.60), and being asked to do something dangerous (AOR 2.25, 95% CI 1.61 to 3.14).
Conclusions: Children are working and being injured in jobs that are not covered by existing child labour laws. Injury rates in non-covered occupations are high, warranting review of current laws.
Aim: To investigate the acute health effects of winter outdoor air pollution (nitrogen dioxide (NO2), ozone (O3), sulphur dioxide (SO2), sulphate (SO42-) ,and particles (PM10)) on schoolchildren in an area of southern England where levels of SO2 had been reported to be high.
Methods: A total of 179 children, aged 7–13, from three schools (two urban and one rural location), were included. Peak expiratory flow rate (PEFR) and presence or absence of upper respiratory infections were recorded on 63 school days from 1 November 1996 to 14 February 1997. Air pollution and meteorological data were taken from monitors at each school site. The analysis regressed daily PEFR on pollutant level adjusting for confounders and serial correlation and calculated a weighted pooled estimate of effect overall for each pollutant. In addition, large decrements in PEFR were analysed as a binary outcome. Same day, lag 1, lag 2, and a five day average of pollutant levels were used.
Results: There were no clear effects of any pollutant on mean PEFR. In addition, we analysed large PEFR decrements (a binary outcome), observing consistent negative associations with NO2, SO42-, and PM10, although few lag/pollutant combinations were significant: odds ratios (95% CI) for five day average effect: NO2 24 h average 1.043 (1.000 to 1.089), SO42- 1.090 (0.898 to 1.322), PM10 1.037 (0.992 to 1.084). The observed effects of PM10 (only) were stronger in wheezy children (1.114 (1.057 to 1.174)). There were no consistent negative associations between large decrements and ozone or SO2 .
Conclusions: There is no strong evidence for acute effects of winter outdoor air pollution on mean PEFR overall in this area, but there is evidence for negative effects on large PEFR decrements.
Background: Uncontrolled studies suggest that psychosocial factors and health behaviour may be important in asthma death.
Methods: A community based case-control study of 533 cases, comprising 78% of all asthma deaths under age 65 years and 533 hospital controls individually matched for age, district and asthma admission date corresponding to date of death was undertaken in seven regions of Britain (1994–98). Data were extracted blind from anonymised copies of primary care records for the previous 5 years and non-blind for the earlier period.
Results: 60% of cases and 63% of controls were female. The median age in both groups was 53. Cases had an earlier age of asthma onset, more chronic obstructive lung disease, and were more obese. 48% of cases and 42% of controls had a health behaviour problem; repeated non-attendance/poor inhaler technique was related to increased risk of death. Overall, 85% and 86%, respectively, had a psychosocial problem. Four psychosocial factors were associated with increased risk of death (psychosis, alcohol/drug abuse, financial/employment problems, learning difficulties) and two with reduced risk (anxiety/prescription of antidepressant drugs and sexual problems). While alcohol/drug abuse lost significance after adjustment for psychosis, other associations appeared independent of each other and of indicators of severity and co-morbidity. None of the remaining 13 factors including family problems, domestic abuse, bereavement, and social isolation were significantly related to risk of asthma death.
Conclusion: There was an apparently high burden of psychosocial problems in both cases and controls. The associations between health behaviour, psychosocial factors, and asthma death are varied and complex with a limited number of factors showing positive relationships.
Objectives: Few published studies have examined the effect of air pollution on upper respiratory conditions. Furthermore, most epidemiological studies on air pollution focus on mortality or hospital admissions as the main health outcomes, but very rarely consider the effect in primary care. If pollution effects do exist then the public health impact could be considerable because of the many patient contacts involved. We investigated the relation between air pollution and upper respiratory disease as reflected in number of consultations made at family practices in London.
Methods: The study used non-parametric methods of analysis of time series data, adjusting for seasonal factors, day of the week, holiday effects, influenza, weather, pollen concentrations, and serial correlation.
Results: It was estimated that a 10–90th percentile change (13–31 µg/m3) in sulphur dioxide (SO2) measures resulted in a small increase in numbers of childhood consultation: 3.5% (95% confidence interval (95% CI 1.4% to 5.8%). Stronger associations were found in the case of a 10–90th percentile change (16–47 µg/m3) in fine particles (PM10) in adults aged 15–64 5.7% (2.9% to 8.6%), and in adults aged 65 and over: 10.2% (5.3% to 15.3%). In general, associations were strongest in elderly people, weakest in the children, and were largely found in the winter months for these two age groups, and in the summer months for adults aged 15–64. An apparent decrease in consultations was associated with ozone concentrations but this was most pronounced in colder months when ozone concentrations were at their lowest.
Conclusions: The results suggest an adverse effect of air pollution on consultations for upper respiratory symptoms, in particular in the case of PM10 and SO2. The effects are relatively small; however, due to the many consultations made in primary care, the impact on demand for services could be considerable.
Objective To investigate the association between bronchodilator treatment and death from asthma.
Design Case-control study.
Setting 33 health authorities or health boards in Great Britain.
Participants 532 patients under age 65 who died from asthma and 532 controls with a hospital admission for asthma matched for period, age, and area.
Main outcome measures Odds ratios for deaths from asthma associated with prescription of bronchodilators and other treatment, with sensitivity analyses adjusting for age at onset, previous hospital admissions, associated chronic obstructive lung disease, and number of other drug categories.
Results After full adjustment, there were no significant associations with drugs prescribed in the 4-12 months before the index date. For prescriptions in the 1-5 years before, mortality was positively associated with inhaled short acting β2 agonists (odds ratio 2.05, 95% confidence interval 1.26 to 3.33) and inversely associated with antibiotics (0.59, 0.39 to 0.89). The former association seemed to be confined to those aged 45-64, and the association with antibiotics was more pronounced in those under 45. Significant age interactions across all periods suggested inverse associations with oral steroids confined to the under 45 age group. An inverse association with long acting β2 agonists and a positive association with methylxanthines in the 1-5 year period were non-significant.
Conclusion There was no evidence of adverse effects on mortality with medium to long term use of inhaled long acting β2 agonist drugs. The association with short acting β2 agonists has several explanations, only one of which may be a direct adverse effect.