Comparing meta-analysis and ecological-longitudinal analysis in time-series studies. A case study of the effects of air pollution on mortality in three Spanish cities

STUDY OBJECTIVE: The objective of this paper is to introduce a different approach, called the ecological-longitudinal, to carrying out pooled analysis in time series ecological studies. Because it gives a larger number of data points and, hence, increases the statistical power of the analysis, this approach, unlike conventional ones, allows the complementation of aspects such as accommodation of random effect models, of lags, of interaction between pollutants and between pollutants and meteorological variables, that are hardly implemented in conventional approaches. DESIGN: The approach is illustrated by providing quantitative estimates of the short-term effects of air pollution on mortality in three Spanish cities, Barcelona, Valencia and Vigo, for the period 1992-1994. Because the dependent variable was a count, a Poisson generalised linear model was first specified. Several modelling issues are worth mentioning. Firstly, because the relations between mortality and explanatory variables were non-linear, cubic splines were used for covariate control, leading to a generalised additive model, GAM. Secondly, the effects of the predictors on the response were allowed to occur with some lag. Thirdly, the residual autocorrelation, because of imperfect control, was controlled for by means of an autoregressive Poisson GAM. Finally, the longitudinal design demanded the consideration of the existence of individual heterogeneity, requiring the consideration of mixed models. MAIN RESULTS: The estimates of the relative risks obtained from the individual analyses varied across cities, particularly those associated with sulphur dioxide. The highest relative risks corresponded to black smoke in Valencia. These estimates were higher than those obtained from the ecological-longitudinal analysis. Relative risks estimated from this latter analysis were practically identical across cities, 1.00638 (95% confidence intervals 1.0002, 1.0011) for a black smoke increase of 10 microg/m(3) and 1.00415 (95% CI 1.0001, 1.0007) for a increase of 10 microg/m(3) of sulphur dioxide. Because the statistical power is higher than in the individual analysis more interactions were statistically significant, especially those among air pollutants and meteorological variables. CONCLUSIONS: Air pollutant levels were related to mortality in the three cities of the study, Barcelona, Valencia and Vigo. These results were consistent with similar studies in other cities, with other multicentric studies and coherent with both, previous individual, for each city, and multicentric studies for all three cities.     

Stapedotomy and anatomical variations of the facial nerve

Among the 595 stapedotomies performed between 1992 and 1999 (surgeon R. H?usler), there were 40 cases (6.7%) where the facial nerve had an abnormal course. In 32, a partial nerve prolapse over the oval window was noted with (6 cases, 1 being a duplicated nerve around the oval window) or without (26 cases) dehiscence in the long bony canal. In 8 cases, there was a total prolapse of the nerve over the oval window, with 2 special cases: facial nerve having an inferior course over the oval window and the promontory; facial nerve being widely spread over the oval window and the promontory. Concomitant anomalies of the stapes were seen and several patients had dysmorphic syndromes with conductive hearing loss since early childhood. Stapedotomy was performed in 39 patients. In the 32 cases of partial nerve prolapse, a small piston (0.4 mm) was placed in the lower part of the oval window which was sometimes enlarged towards the promontory, except when the nerve was duplicated: the prosthesis was placed into the footplate between the nerve branches. In the 8 patients with total facial nerve prolapse, the prosthesis was either placed directly in a burr hole into the promontory just below the oval window (6 cases), or, when the nerve ran over the promontory and over the oval window, the prosthesis was placed above the oval window at the site where the facial nerve is usually located (1 case). In the case where the nerve was spread widely over the oval window and the promontory, no prosthesis was placed. In the 39 patients where a stapedotomy was performed, the average hearing level gain ranged from -15 dB to 40 dB (average: 18 dB) at 0.5, 1, 2 and 4 kHz. The average residual air-bone gap was < 30 dB in 36 patients (92.3%), < 20 dB in 30 (77%) and < 10 dB in 16 (41%). A post-operative additional hearing loss > or = 10 dB occurred in 3 cases (10, 12.5 and 12.5 dB). There were no cases of post-operative deafness or facial palsy. This analysis shows that in many cases with an aberrant course of the facial nerve, stapedotomy using adequate and sometimes non-conventional techniques can give post-operative hearing improvement.     

Massive hemoptysis: what place for medical and surgical treatment.

OBJECTIVE: The objective of the study was to define timing of surgical treatment in management of massive hemoptysis. METHODS: We performed a retrospective review of all patients admitted for massive hemoptysis in the intensive care unit of our thoracic surgery department. Treatment was managed according to the patient's status, the etiology of bleeding, the findings of bronchoscopy and computed tomographic scan. Therapeutic measures available were medical treatment, tracheal intubation (single or double lumen tube), interventional endoscopy, arterial embolisation and surgical treatment. RESULTS: Between September 1996 and December 2001, 43 patients were treated (nine females and 34 males with mean age of 54 years, range from 32 to 79). The mean red cell blood transfusion per patient was 1.57 Units. The patients were classified into three groups: Group 1, 11 patients were operated on immediately close to the bleeding crise (five pneumonectomy and six lobectomy); Group 2, five patients for whom operation was delayed from the 7th to the 22nd day after cessation of bleeding (five lobectomy); Group 3, 27 patients were treated by non-surgical methods (medical treatment, endobronchial treatment, percutaneous embolisation). Fifteen patients underwent an arterial embolization, which was complete in 13 cases. Among the five patients of group 2, cessation of bleeding was obtained by bronchial embolisation in four cases. Considering the whole series, 10 (23%) patients died: three (19%) patients in group 1, zero in group 2, seven (26%) in group 3. In two patients who were suffering from tumor necrosis, hemoptysis relapsed leading to death. CONCLUSION: Emergency thoracotomy for massive hemoptysis is at high risk. In case of bleeding from the arterial bronchial vessels, embolization may enable to postpone surgery and operate secondarily. In case of bleeding from the pulmonary vessels (tumor necrosis), surgical treatment must be immediate. An algorithm for management is proposed.     

Effect of nifedipine on arterial hypoxaemia occurring after methacholine challenge in asthma.

To investigate whether the effects of nifedipine on methacholine induced broncho-constriction could impair pulmonary gas exchange in bronchial asthma a randomised, double blind, crossover study in 13 symptom free asthmatic subjects was designed. Each patient underwent a methacholine bronchial challenge test on two separate days one week apart, after having either oral nifedipine (20 mg thrice daily) or placebo for three days. Arterial blood gases were measured before and after methacholine challenge in nine subjects. Prechallenge values of forced expiratory volume in one second (FEV1) and arterial oxygen tension (Pao2) were similar after nifedipine and after placebo. After challenge, the cumulative doses of methacholine required to produce a 20% fall in FEV1 (PD20 FEV1) were significantly larger after nifedipine (280 (SD 347)) cumulative breath units (CBU) than after placebo (120 (183) CBU; p less than 0.01). After challenge the fall in Pao2 values (17.1 (1.6) mm Hg; (2.28 (0.21) kPa)) was significantly greater than after placebo (11.7 (2.4) mm Hg; (1.56 (0.32) kPa) p less than 0.03). Our data show that although oral nifedipine significantly reduces airway reactivity in patients with mild bronchial asthma, it also adversely affects pulmonary gas exchange, resulting in a lowered postchallenge Pao2, probably because of worsening ventilation-perfusion relationships.     

Association between hospital emergency visits for asthma and air pollution in Valencia,Spain

OBJECTIVE: To assess the short term effect of concentrations of black smoke, sulphur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3) in ambient air on emergency room visits for asthma in the city of Valencia, Spain during the period 1994-5. METHODS: Ecological study with time series data and application of Poisson regression. Associations between number of daily emergency visits in a city''s hospital and concentrations of air pollutants were analysed taking into account potential confounding factors by the standardised protocol of the air pollution and health: a European approach (APHEA) project. RESULTS: Mean (range) daily number of emergency room visits for asthma was 1 (0-5). Concentrations of all pollutants studied remained within current air quality standards. The association between an increase of 10 micrograms/m3 in ambient air pollution and asthma, measured as a relative risk (RR) of emergency visits, was significant for NO2 24 hour mean (lag 0, RR 1.076, 95% confidence interval (95% CI) 1.020 to 1.134), NO2 hour maximum (lag 0, RR 1.037, 95% CI 1.008 to 1.066), and O3 hour maximum (lag 1, RR 1.063, CI 95% 1.014 to 1.114). The association was not significant for SO2 or for black smoke during the period analysed. The effects were not significantly different for the time of year, cold months (November to April), or warm months (May to October). CONCLUSIONS: Current concentrations of ambient air pollution in Valencia are significantly associated with emergency room visits for asthma. This association is high and more consistent for NO2 and O3 than for particulate matter and SO2 (classic pollutants).       

Estimate of daily cases of influenza from the cases notified to the Reportable Disease System: usefulness in time series studies]

In time series analyses assessing the relationship between risk factors and respiratory diseases or mortality, influenza incidence is a potential cofounder and, therefore, must be controlled. Available influenza data come from weekly compulsory notifiable disease (EDO system). Furthermore, its graphical distribution, suggests that information may be underestimated in holiday periods. We have applied a procedure for estimate daily influenza series from the weekly cases, using less, a non-parametric local fit. Findings show that smoothing could avoid stepping and sudden peaks in the original series.     

A review of original papers that analyze the effects of air pollution on mortality, 1994-1998]

The different studies published and indexed in Medline and in the Spanish Medical Index (IME) from 1984 up to 1998 (IME: 1971-1996) are reviewed. To start with, an assessment was made of the number of publications put out which have to do with the impact of pollution on human health as well as the percentage thereof which analyze the mortality as a health indicator. Afterward, the original works published within the January 1994-June 1998 period were reviewed in detail. Most of the original articles are combined time series studies which analyze, on a single-day basis, the relationship between the levels of pollution and the mortality for non-accidental causes. Other original articles were also summarized based on an approach other than the time series one, highlighting different cohort studies which relate the levels of pollution to the mortality on an individual level and which confirm the findings of prior ecological studies. The pollutants analyzed most often are the different types of particles, although studies are also common regarding the impact of sulfur dioxide, nitrogen dioxide, ozone and carbon monoxide. The method of analysis most used is the Poisson regression, into which different confusion variables bearing an impact thereon such as seasonality and tendency, temperature and relative humidity and day of the year are basically added. In the studies reviewed, the positive significant findings prevail, being consistent especially for particles, which is the pollutant most analyzed. The articles studying other pollutants, although fewer in number, also indicate a significant relationship between pollution levels and the mortality.     

Apoptosis and gamma rays]

Gamma radiation can induce cell death in lymphocytes. Apoptosis is characterized by numerous morphological, biochemical and molecular modifications measurable using various methods. Some radioprotectors have antioxidant properties and are able to inhibit radiation-induced DNA fragmentation and caspase activation. There are several caspases that cleave proteolytically many proteins and trigger phosphatidylserine externalization recognized by phagocytes. Three main proteins are involved in the regulation of radiation-induced apoptosis: p53, Fas and Bcl-2. The pharmacological regulation of cell death is discussed in order to investigate the subsequent effects related to cell regeneration following radiation injury.