Observational studies: practical tips for avoiding common statistical pitfalls.

This Personal View is intended for early-career researchers who are not yet experts in statistics. The Personal View focuses on common but usually avoidable flaws in the context of observational studies. I point out how study design, data collection, and statistical methods impact statistical results and research conclusions. With particular attention to study planning, sample selection, biases, lack of transparency and results misinterpretations.

Electric field and air ion exposures near high voltage overhead power lines and adult cancers: a case control study across England and Wales.

BACKGROUND: Various mechanisms have been postulated to explain how electric fields emitted by high voltage overhead power lines, and the charged ions they produce, might be associated with possible adult cancer risk, but this has not previously been systematically explored in large scale epidemiological research. METHODS: We investigated risks of adult cancers in relation to modelled air ion density (per cm3) within 600 m (focusing analysis on mouth, lung, respiratory), and calculated electric field within 25 m (focusing analysis on non-melanoma skin), of high voltage overhead power lines in England and Wales, 1974-2008. RESULTS: With adjustment for age, sex, deprivation and rurality, odds ratios (OR) in the highest fifth of net air ion density (0.504-1) compared with the lowest (0-0.1879) ranged from 0.94 [95% confidence interval (CI) 0.82-1.08] for mouth cancers to 1.03 (95% CI 0.97-1.09) for respiratory system cancers, with no trends in risk. The pattern of cancer risk was similar using corona ion estimates from an alternative model proposed by others. For keratinocyte carcinoma, adjusted OR in the highest (1.06-4.11 kV/m) compared with the lowest (<0.70 kV/m) thirds of electric field strength was 1.23 (95% CI 0.65-2.34), with no trend in risk. CONCLUSIONS: Our results do not provide evidence to support hypotheses that air ion density or electric fields in the vicinity of power lines are associated with cancer risk in adults.

Risk of respiratory hospital admission associated with modelled concentrations of Aspergillus fumigatus from composting facilities in England.

Bioaerosols have been associated with adverse respiratory-related health effects and are emitted in elevated concentrations from composting facilities. We used modelled Aspergillus fumigatus concentrations, a good indicator for bioaerosol emissions, to assess associations with respiratory-related hospital admissions. Mean daily Aspergillus fumigatus concentrations were estimated for each composting site for first full year of permit issue from 2005 onwards to 2014 for Census Output Areas (COAs) within 4 km of 76 composting facilities in England, as previously described (Williams et al., 2019). We fitted a hierarchical generalized mixed model to examine the risk of hospital admission with a primary diagnosis of (i) any respiratory condition, (ii) respiratory infections, (iii) asthma, (iv) COPD, (v) diseases due to organic dust, and (vi) Cystic Fibrosis, in relation to quartiles of Aspergillus fumigatus concentrations. Models included a random intercept for each COA to account for over-dispersion, nested within composting facility, on which a random intercept was fitted to account for clustering of the data, with adjustments for age, sex, ethnicity, deprivation, tobacco sales (smoking proxy) and traffic load (as a proxy for traffic-related air pollution). We included 249,748 respiratory-related and 3163 Cystic Fibrosis hospital admissions in 9606 COAs with a population-weighted centroid within 4 km of the 76 included composting facilities. After adjustment for confounders, no statistically significant effect was observed for any respiratory-related (Relative Risk (RR) = 0.99; 95% Confidence Interval (CI) 0.96-1.01) or for Cystic Fibrosis (RR = 1.01; 95% CI 0.56-1.83) hospital admissions for COAs in the highest quartile of exposure. Similar results were observed across all respiratory disease sub-groups. This study does not provide evidence for increased risks of respiratory-related hospitalisations for those living near composting facilities. However, given the limitations in the dispersion modelling, risks cannot be completely ruled out. Hospital admissions represent severe respiratory episodes, so further study would be needed to investigate whether bioaerosols emitted from composting facilities have impacts on less severe episodes or respiratory symptoms.

Birth weight trends in England and Wales (1986-2012): babies are getting heavier.

INTRODUCTION: Birth weight is a strong predictor of infant mortality, morbidity and later disease risk. Previous work from the 1980s indicated a shift in the UK towards heavier births; this descriptive analysis looks at more recent trends. METHODS: Office for National Statistics (ONS) registration data on 17.2 million live, single births from 1986 to 2012 were investigated for temporal trends in mean birth weight, potential years of birth weight change and changes in the proportions of very low (<1500 g), low (<2500 g) and high (≥4000 g) birth weight. Analysis used multiple linear and logistic regression adjusted for maternal age, marital status, area-level deprivation and ethnicity. Additional analyses used the ONS NHS Numbers for Babies data set for 2006-2012, which has information on individual ethnicity and gestational age. RESULTS: Over 27 years there was an increase in birth weight of 43 g (95% CI 42 to 44) in females and 44 g (95% CI 43 to 45) in males, driven by birth weight increases between 1986-1990 and 2007-2012. There was a concurrent decreased risk of having low birth weight but an 8% increased risk in males and 10% increased risk in females of having high birth weight. For 2006-2012 the birth weight increase was greater in preterm as compared with term births. CONCLUSIONS: Since 1986 the birth weight distribution of live, single births in England and Wales has shifted towards heavier births, partly explained by increases in maternal age and non-white ethnicity, as well as changes in deprivation levels. Other potential influences include increases in maternal obesity and reductions in smoking prevalence particularly following the introduction of legislation restricting smoking in public places in 2007.

Prediction of Fetal Growth Restriction by Analyzing the Messenger RNAs of Angiogenic Factor in the Plasma of Pregnant Women.

OBJECTIVE: To predict the occurrence of fetal growth restriction (FGR) by analyzing messenger RNA (mRNA) expression levels of vascular endothelial growth factor receptor 1 (fms-like tyrosine kinase 1 [Flt-1]) in maternal blood. STUDY DESIGN: Eleven women with FGR were matched with 88 controls. Plasma samples were obtained during each trimester. The Flt-1 mRNA expression levels were compared between groups. Predicted probabilities were calculated, and sensitivity-specificity (receiver-operating characteristic [ROC]) curves were assessed based on regression models for each trimester measurement and possible combinations of measurements. RESULTS: The mRNA levels of the FGR group during all trimesters were significantly higher than those of the control group. The ROC curve of combined first and second trimester data yielded a detection rate of 60% at a 10% false-positive rate, with an area under curve of 0.79. CONCLUSION: The Flt-1 mRNA expression in maternal blood can be used as a marker to predict the development of FGR, long before a clinical diagnosis is made.

Air pollution from incinerators and reproductive outcomes: a multisite study.

BACKGROUND: The few studies that have investigated the relationship between emissions from municipal solid-waste incinerators and adverse pregnancy outcomes have had conflicting results. We conducted a study to assess the effects of air emissions from the eight incinerators currently in operation in the Emilia-Romagna Region of Italy on reproductive outcomes (sex ratio, multiple births, preterm births, and small for gestational age [SGA] births). METHODS: We considered all births (n = 21,517) to women residing within a 4-km radius of an incinerator at the time of delivery during the period 2003-2010 who were successfully linked to the Delivery Certificate database. This source also provided information on maternal characteristics and deliveries. Each newborn was georeferenced and characterized by a specific level of exposure to incinerator emissions, categorized in quintiles of PM10, and other sources of pollution (NOx quartiles), evaluated by means of ADMS-Urban system dispersion models. We ran logistic regression models for each outcome, adjusting for exposure to other pollution sources and maternal covariates. RESULTS: Incinerator pollution was not associated with sex ratio, multiple births, or frequency of SGA. Preterm delivery increased with increasing exposure (test for trend, P < 0.001); for the highest versus the lowest quintile exposure, the odds ratio was 1.30 (95% confidence interval = 1.08-1.57). A similar trend was observed for very preterm babies. Several sensitivity analyses did not alter these results. CONCLUSIONS: Maternal exposure to incinerator emissions, even at very low levels, was associated with preterm delivery.

Volume reduction of cystic lesions after surgical decompression: a computerised three-dimensional computed tomographic evaluation.

OBJECTIVES: This study was performed to evaluate the three-dimensional radiographic variation in mandibular odontogenic cystic lesions after decompression. MATERIALS AND METHODS: Pre- and post-decompression computed tomography (CT) evaluations in 20 patients affected by keratocysts (n = 10), dentigerous cysts (n = 9) and ameloblastoma (n = 1) were analysed using software designed for three-dimensional measurement of volumes; the results were correlated with treatment duration, age, sex and histological type. RESULTS: The mean (range) decompression time was 5.70 (3-12) months. The mean (SD) pre- and post-decompression volumes were 9.50 (7.74) and 4.65 (4.34) cm(3), respectively (P < 0.001), with a mean (SD) reduction of 49.86 % (19.34 %). The volume reduction was positively correlated with the duration of decompression (P < 0.001), whereas no correlations with other variables were found (P = 0.2357). The median monthly reduction in cyst volume was 11.34 % (mean, 13.52 %; range, 4.45-30.43 %) (P < 0.001). CONCLUSIONS: This three-dimensional CT investigation demonstrated the effectiveness of decompression in the treatment of mandibular odontogenic cystic lesions and showed a positive correlation between the duration of treatment and volume reduction. CLINICAL RELEVANCE: Decompression treatment, which is simple to perform and generally well-accepted by patients, is a reliable method to considerably reduce the volume of mandibular odontogenic cystic lesions before surgical removal. Extended decompression time seems to improve results of the reduction process.

Science in drug control: the alkaloid content of afghan opium.

Opium samples from Afghanistan were analyzed by HPLC for their content of morphine and three further alkaloids (codeine, thebaine, and papaverine). To our knowledge, this is the largest set of authentic opium samples analyzed in one study until now. The purpose was to assess possible correlations between samples and selected external factors, such as region of origin within Afghanistan, year of harvest, or intra-batch variation. In the investigated samples, a trend towards higher morphine concentrations in opium from the North-Eastern parts of Afghanistan was observed in the period from 2003 to 2005. More than 75% of the samples contained above 10% of morphine, the overall average was 14.4%.