[Medical biostatistics with GMRC Shiny Stats - learning by doing]. / Biostatistiques médicales avec GMRC Shiny Stats ­ un outil de formation par la pratique.

Biostatistics are omnipresent in the scientific and medical literature and are an essential skill for any health student. We have developed a practical training tool - GMRC Shiny stats - an interactive application specifically dedicated to medical data statistical analysis. The application has been designed to provide an analysis workflow corresponding to the usual progression of an experienced statistician during data analysis. The most common statistical analyses can be performed (descriptive statistics, inferences according to frequentist methods, survival analyses, correlation, agreement measurements, etc.). GMRC Shiny stats is intuitive and user-friendly and assists students in choosing the most appropriate statistical tests. With all these functionalities, students can learn statistical analysis by doing. Getting involved in the statistical analysis and processing of their own data is likely to improve their biostatistics skills.

Reliability, factor analysis and internal consistency calculation of the Insomnia Severity Index (ISI) in French and in English among Lebanese adolescents.

OBJECTIVES: Our goal is to validate and to verify the reliability of the French and English versions of the Insomnia Severity Index (ISI) in Lebanese adolescents. STUDY DESIGN: A cross-sectional study was implemented. METHODS: 104 Lebanese students aged between 14 and 19 years participated in the study. The English version of the questionnaire was distributed to English-speaking students and the French version was administered to French-speaking students. A scale (1 to 7 with 1 = very well understood and 7 = not at all) was used to identify the level of the students' understanding of each instruction, question and answer of the ISI. The scale's structural validity was assessed. The factor structure of ISI was evaluated by principal component analysis. The internal consistency of this scale was evaluated by Cronbach's alpha. To assess test-retest reliability the intraclass correlation coefficient (ICC) was used. RESULTS: The principal component analysis confirmed the presence of a two-component factor structure in the English version and a three-component factor structure in the French version with eigenvalues > 1. The English version of the ISI had an excellent internal consistency (α = 0.90), while the French version had a good internal consistency (α = 0.70). The ICC presented an excellent agreement in the French version (ICC = 0.914, CI = 0.856-0.949) and a good agreement in the English one (ICC = 0.762, CI = 0.481-890). The Bland-Altman plots of the two versions of the ISI showed that the responses over two weeks' were comparable and very few outliers were detected. CONCLUSION: The results of our analyses reveal that both English and French versions of the ISI scale have good internal consistency and are reproducible and reliable. Therefore, it can be used to assess the prevalence of insomnia in Lebanese adolescents.

Tailored telephone counselling to increase participation of underusers in a population-based colorectal cancer-screening programme with faecal occult blood test: A randomized controlled trial.

BACKGROUND: Despite the involvement of general practitioners, the mailing of several recall letters and of the faecal occult blood test (FOBT) kit, the uptake remains insufficient in the French colorectal cancer-screening programme. Some studies have demonstrated a greater efficacy of tailored telephone counselling over usual care, untailored invitation mailing and FOBT kit mailing. We evaluated the feasibility and the effectiveness of telephone counselling on participation in the population-based FOBT colorectal cancer-screening programme implemented in Alsace (France). METHODS: Underusers were randomized into a control group with untailored invitation and FOBT kit mailing (n=19,756) and two intervention groups for either a computer-assisted telephone interview (n=9367), system for tailored promotion of colorectal cancer screening, or a telephone-based motivational interview (n=9374). RESULTS: Only 5691 (19.9%) people were actually counseled, so that there was no difference in participation between the intervention groups taken together (13.9%, 95% confidence interval [CI] [13.5-14.4]) and the control group (13.9%, 95% CI [13.4-14.4]) (P=1.0) in intent-to-treat analysis. However, in per-protocol analysis, participation was significantly higher in the two intervention groups than in the control group (12.9%, 95% CI [12.6-13.2]) (P<0.01), with no difference between computer-assisted telephone interview (24.6%, 95% CI [22.7-26.4]) and motivational interview (23.6%, 95% CI [21.8-25.4]) (P=0.44). CONCLUSION: There was no difference of effectiveness between tailored telephone counselling and untailored invitation and FOBT kit mailing on participation of underusers in an organized population-based colorectal cancer screening programme. A greater efficacy of telephone counselling, around twice that of invitation and FOBT kit mailing, was observed only in people who could actually be counseled, without difference between computer-assisted telephone interview and motivational interview. However, technical failures hampered telephone counselling, so that there was no difference in intent-to-treat analysis. The rate of technical success of telephone interviews should be evaluated, and enhanced if insufficient, before implementation of telephone counselling in population-based cancer screening programmes.

Cervical sagittal alignment in adult hyperkyphosis treated by posterior instrumentation and in situ bending.

BACKGROUND: In the normal adult spine, a link between thoracolumbar and cervical sagittal alignment exists, suggesting adaptive cervical positional changes allowing horizontal gaze. In patients with thoracic hyperkyphosis, cervical adaptation to sagittal global alignment might be different from healthy individuals. However, this relationship has not clearly been reported in hyperkyphotic deformity. PURPOSE: The purpose of this study was to identify cervical sagittal alignment types observed on radiographs in young adults with thoracic hyperkyphosis. The relationship between cervical and thoracolumbar alignment as well as the effect of posterior instrumentation and adaptive positional changes of the mobile cervical segment were retrospectively analyzed. PATIENTS AND METHODS: Twenty-three patients (32.7 years; 5-year follow-up) were included. Full spine radiographic measurements were: T1 slope, T1-T4 kyphosis, T4-T12 kyphosis, L1-S1 lordosis, pelvic incidence, pelvic tilt, sacral slope, SVA C7, SVA C2, lordosis between C0-C2, C2-C7, C2-C4 and C4-C7. A Bayesian model and Spearman correlation were used. RESULTS: Two alignment types existed: cervical lordosis (group A) and cervical kyphosis (group B). Preoperatively, T4-T12 kyphosis and L1-S1 lordosis were significantly higher in group A: 76.6° versus 59.4° and -72.8° versus -65.8° (probability of>5° difference P (ß>5)>0.95). Pelvic incidence was higher in group A (49.8° versus 44.2°) and C0-C2 lordosis in group B (-29.4° versus -21.6°). A significant correlation existed between: T4-T12 kyphosis and C2-C7 lordosis, L1-S1 lordosis and pelvic incidence, C2-C7 lordosis and T1 slope, C2-C7 lordosis and T1-T4 kyphosis. Postoperatively, T4-T12 kyphosis decreased by 33.1° P (ß>5)=0.9995), L1-S1 lordosis decreased by 17.7° (P (ß>5)=0.961), T1-T4 kyphosis increased by 14.1° (P (ß>5)=0.973). SVA C2 (translation) increased by 13.8mm. C0-C2 lordosis (head rotation) remained unchanged. Six patients changed cervical alignment. PJK occurred in 15 patients, unrelated to cervical alignment or proximal instrumentation level. DISCUSSION: Two cervical alignment types, lordotic or kyphotic, were observed thoracic hyperkyphosis patients. This alignment was mainly triggered by the amount of thoracic kyphosis and lumbar lordosis, linked to pelvic incidence. Moreover, the inclination of the C7-T1 junctional area plays a key role in the amount of cervical lordosis. The correction of T4-T12 kyphosis induced compensatory modifications at adjacent segments: T1-T4 kyphosis increase (PJK) and L1-S1 lordosis decrease. Global spino-pelvic alignment and head position did not change in the sagittal plane. The cervical spine tented to keep in its preoperative position in most patients. LEVEL OF EVIDENCE: Level IV.

Pullout characteristics of percutaneous pedicle screws with different cement augmentation methods in elderly spines: An in vitro biomechanical study.

BACKGROUND: Vertebroplasty prefilling or fenestrated pedicle screw augmentation can be used to enhance pullout resistance in elderly patients. It is not clear which method offers the most reliable fixation strength if axial pullout and a bending moment is applied. The purpose of this study is to validate a new in vitro model aimed to reproduce a cut out mechanism of lumbar pedicle screws, to compare fixation strength in elderly spines with different cement augmentation techniques and to analyze factors that might influence the failure pattern. MATERIALS AND METHODS: Six human specimens (82-100 years) were instrumented percutaneously at L2, L3 and L4 by non-augmented screws, vertebroplasty augmentation and fenestrated screws. Cement distribution (2 ml PMMA) was analyzed on CT. Vertebral endplates and the rod were oriented at 45° to the horizontal plane. The vertebral body was held by resin in a cylinder, linked to an unconstrained pivot, on which traction (10 N/s) was applied until rupture. Load-displacement curves were compared to simultaneous video recordings. RESULTS: Median pullout forces were 488.5 N (195-500) for non-augmented screws, 643.5 N (270-1050) for vertebroplasty augmentation and 943.5 N (750-1084) for fenestrated screws. Cement augmentation through fenestrated screws led to significantly higher rupture forces compared to non-augmented screws (P=0.0039). The pullout force after vertebroplasty was variable and linked to cement distribution. A cement bolus around the distal screw tip led to pullout forces similar to non-augmented screws. A proximal cement bolus, as it was observed in fenestrated screws, led to higher pullout resistance. This cement distribution led to vertebral body fractures prior to screw pullout. CONCLUSION: The experimental setup tended to reproduce a pullout mechanism observed on radiographs, combining axial pullout and a bending moment. Cement augmentation with fenestrated screws increased pullout resistance significantly, whereas the fixation strength with the vertebroplasty prefilling method was linked to the cement distribution.

The effect of posterior non-fusion instrumentation on segmental shear loading of the lumbar spine.

BACKGROUND: Lumbar stenosis and facet osteoarthritis represent indications for decompression and instrumentation. It is unclear if degenerative spondylolisthesis grade I with a remaining disc height could be an indication for non-fusion instrumentation. The purpose of this study was to determine the influence of a mobile pedicle screw based device on lumbar segmental shear loading, thus simulating the condition of spondylolisthesis. MATERIALS AND METHODS: Six human cadaver specimens were tested in 3 configurations: intact L4-L5 segment, then facetectomy plus undercutting laminectomy, then instrumentation with lesion. A static axial compression of 400 N was applied to the lumbar segment and anterior displacements of L4 on L5 were measured for posterior-anterior shear forces from 0 to 200 N. The slope of the loading curve was assessed to determine shear stiffness. RESULTS: Homogenous load-displacement curves were obtained for all specimens. The average intact anterior displacement was 1.2 mm. After lesion, the displacement increased by 0.6mm compared to intact (P=0.032). The instrumentation decreased the displacement by 0.5 mm compared to lesion (P=0.046). The stiffness's were: 162 N/mm for intact, 106 N/mm for lesion, 148 N/mm for instrumentation. The difference was not significant between instrumented and intact segments (P=0.591). CONCLUSIONS: Facetectomy plus undercutting laminectomy decreases segmental shear stiffness and increases anterior translational L4-L5 displacement. Shear stiffness of the instrumented segment is higher with the device and anterior displacements under shear loading are similar to the intact spine. This condition could theoretically be interesting for the simulation of non-fusion instrumentation in degenerative spondylolisthesis.

[Hereditary hemochromatosis: presenting manifestations and diagnostic delay]. / Hémochromatose héréditaire: circonstances de découverte et délais diagnostiques.

PURPOSE: Hereditary hemochromatosis is characterized by an excessive absorption and progressive accumulation of iron in the liver, the pancreas, the heart, and the joints. Tiredness and joint manifestations occur usually before hepatopathy, diabetes or cardiopathy. Such common and unspecific symptoms seem to be largely unknown and important diagnostic delays have been reported. The aim of this study was to investigate the discovery circumstances and the diagnostic delay. METHODS: A survey was carried out amongst French patients with C282Y homozygous hemochromatosis who were contacted through patients associations or blood centers. RESULTS: The questionnaire was answered by 374 patients. Mean age at diagnosis was 48.6±11.9years. In 53% of the cases, the serum level of ferritin was greater than 1000 µg/L. Diagnosis was based on family genetic survey (29%), or fortuitous analyses showing an abnormal serum ferritin (26%), or clinical manifestations (45%). Main complaints were joint pain, tiredness or liver disease. Only 2.1% consulted for diabetes, cardiopathy or changed complexion. Time to diagnosis was lower than 1 year for 98% of patients who presented with fatigue but from 1 to 15 years for 23.4% and 29% of patients who presented with arthropathy and hepatopathy, respectively. CONCLUSION: For 55% of patients, diagnosis was based on familial genetic survey or fortuitous abnormal results of blood samples. An initial serum level of ferritin greater than 1000 µg/L was a factor of severity for 50% of patient. These two elements must be taken into account to consider a population mass screening. Long time to diagnosis required a sensitization of the population to be aware of the clinical manifestations of hemochromatosis.

How to interpret and choose a Bayesian spatial model and a Poisson regression model in the context of describing small area cancer risks variations.

BACKGROUND: The statistical Bayesian approach is widely used in disease mapping and Poisson regression. Results differ depending on the underlying hypothesis. Our objective is to give a comprehensive presentation of the tools that can be used to interpret results and choose between the different hypotheses. Data from the Isere cancer registry (France) illustrate this presentation. METHOD: We consider, first, Bayesian models for disease mapping. Classic heterogeneity (Potthoff-Whithinghill statistic) and spatial autocorrelation tests (Moran statistic) of the SIRs, the DIC criteria of the different Bayesian models and finally the comparison of the empirical variance of the unstructured and structured heterogeneity components of the BYM model are considered. The last two criteria are considered for Bayesian Poisson regression including a covariate. Mapping the components of the BYM model with a covariate is also considered. RESULTS: Four cancer sites (prostate, lung, colon-rectum and bladder) in men diagnosed during the 1998-2007 period are used to illustrate our presentation. We show that the different criteria used to interpret and to choose a model give coherent results. CONCLUSION: A relevant interpretation of results is a necessary step in choosing the best-adapted Bayesian model. This choice is easy to make with criteria such as the DIC. The comparison of the empirical variance of the unstructured and structured heterogeneity components of the BYM model is also informative.

[Obstetric and neonatal outcomes in a home-like birth centre: a case-control study]. / Issues obstétricales et néonatales en « maison de la naissance ¼ : une étude cas-témoins.

OBJECTIVES: To compare intervention rates associated with labor in low-risk women who began their labor in the "home-like birth centre" and the traditional delivery room. PATIENTS AND METHODS: This retrospective study used data that were collected from January 2005 through June 2008, from women admitted to the "home-like birth centre" (n=316) and compared to a group of randomly selected low-risk women admitted to the traditional labor ward (n=890) using the Baysian Information Criterion to select the best predictive model. RESULTS: Women in the "home-like birth centre" had spontaneous vaginal deliveries more often (88.6% versus 82.8%, P value 0.034) and perineal lesions less often (60.1% versus 62.5%, P value 0.013). The frequency of adverse neonatal outcomes did not differ statistically between the two groups, although mean clamped at birth umbilical arterial pH level was higher in the "home-like birth centre" group. The transfer rate from "home-like birth centre" to traditional labor ward was 31.3%. DISCUSSION AND CONCLUSIONS: It appears that women could benefit from "home-like birth centre" care in settings such as the one studied. Larger observational studies are warranted to validate these results.

Evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005.

The evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005 was analysed using data derived from the French network of cancer registries (FRANCIM) and the French National Mesothelioma Surveillance Program (PNSM). Mesothelioma proportions in pleural cancers were calculated by diagnosis year in the 1980-2000 period. Our results suggest that the incidences of pleural cancer and mesothelioma levelled off in French men since 2000 and continued to increase in French women. A decrease of the annual pleural cancer incidence average in men was noticed (-3.4% of annual rate of change) between 2000 and 2005. The proportion of pleural cancers that were mesothelioma was unchanged between 1980 and 2003 with an average of 86%. The age standardised incidence rate of pleural mesothelioma remained relatively stable between 1998 and 2005 with a slight falling trend. For women, the age standardised incidence rate of pleural cancers and mesothelioma increased during the period 1998-2005. Additionally, the proportion of pleural cancers that were mesothelioma increased during the same period of time. Finally, the increased trend observed in the incidence of pleural mesothelioma and cancers in women is credibly due to their under diagnosis in the 1980-1997 period. The comparison between the French incidence and the American and British ones shows that the decreasing trend in incidence of mesothelioma and pleural cancers in French men since 2000 is potentially associated with a lower amphibole consumption and by the implementation of safety regulations at work from 1977.

Socioeconomic and geographic determinants of survival of patients with digestive cancer in France.

Using a multilevel Cox model, the association between socioeconomic and geographical aggregate variables and survival was investigated in 81 268 patients with digestive tract cancer diagnosed in the years 1980-1997 and registered in 12 registries in the French Network of Cancer Registries. This association differed according to cancer site: it was clear for colon (relative risk (RR)=1.10 (1.04-1.16), 1.10 (1.04-1.16) and 1.14 (1.05-1.23), respectively, for distances to nearest reference cancer care centre between 10 and 30, 30 and 50 and more than 90 km, in comparison with distance of less than 10 km; P-trend=0.003) and rectal cancer (RR=1.09 (1.03-1.15), RR=1.08 (1.02-1.14) and RR=1.12 (1.05-1.19), respectively, for distances between 10 and 30 km, 30 and 50 km and 50 and 70 km, P-trend=0.024) (n=28 010 and n=18 080, respectively) but was not significant for gall bladder and biliary tract cancer (n=2893) or small intestine cancer (n=1038). Even though the influence of socioeconomic status on prognosis is modest compared to clinical prognostic factors such as histology or stage at diagnosis, socioeconomic deprivation and distance to nearest cancer centre need to be considered as potential survival predictors in digestive tract cancer.

Combining expert ratings and exposure measurements: a random effect paradigm.

The aim of this paper is to present a paradigm for combining ordinal expert ratings with exposure measurements while accounting for a between-worker effect when estimating exposure group (EG)-specific means for epidemiological purposes. Expert judgement is used to classify the EGs into a limited number of exposure levels independently of the exposure measurements. The mean exposure of each EG is considered to be a random deviate from a central exposure rating-specific value. Combining this approach with the standard between-worker random effect model, we obtain a nested two-way model. Using Gibbs sampling, we can fit such models incorporating prior information on components of variance and modelling options to the rating-specific means. An approximate formula is presented estimating the mean exposure of each EG as a function of the geometric mean of the measurements in this EG, between and within EG standard deviations and the overall geometric mean, thus borrowing information from other EGs. We apply this paradigm to an actual data set of dust exposure measurements in a steel producing factory. Some EG-specific means are quite different from the estimates including the ratings. Rating-specific means could be estimated under different hypotheses. It is argued that when setting up an expert rating of exposures it is best done independently of existing exposure measurements. The present model is then a convenient framework in which to combine the two sources of information.

Dose-response slope of forced oscillation and forced expiratory parameters in bronchial challenge testing.

In population studies, the provocative dose (PD) of bronchoconstrictor causing a significant decrement in lung function cannot be calculated for most subjects. Dose-response curves for carbachol were examined to determine whether this relationship can be summarized by means of a continuous index likely to be calculable for all subjects, namely the two-point dose response slope (DRS) of mean resistance (Rm) and resistance at 10 Hz (R10) measured by the forced oscillation technique (FOT). Five doses of carbachol (320 microg each) were inhaled by 71 patients referred for investigation of asthma (n=16), chronic cough (n=15), nasal polyposis (n=8), chronic rhinitis (n=8), dyspnoea (n=8), urticaria (n=5), post-anaphylactic shock (n=4) and miscellaneous conditions (n=7). FOT resistance and forced expiratory volume in one second (FEV1) were measured in close succession. The PD of carbachol leading to a fall in FEV1 > or = 20% (PD20) or a rise in Rm or R10 > or = 47% (PD47,Rm and PD47,R10) were calculated by interpolation. DRS for FEV1 (DRSFEV1), Rm (DRSRm) and R10 (DRSR10) were obtained as the percentage change at last dose divided by the total dose of carbachol. The sensitivity (Se) and specificity (Sp) of DRSRm, DRS10 delta%Rm and delta%R10 in detecting spirometric bronchial hyperresponsiveness (BHR, fall in FEV1 > or = 20%) were assessed by receiver operating characteristic (ROC) curves. There were 23 (32%) "spirometric" reactors. PD20 correlated strongly with DRSFEV1 (r=-0.962; p=0.0001); PD47,Rm correlated significantly with DRSRm (r=-0.648; p=0.0001) and PD47,R10 with DRSR10 (r=-0.552; p=0.0001). DRSFEV1 correlated significantly with both DRSRm (r=0.700; p=0.0001) and DRSR10 (r=0.784; p=0.0001). The Se and Sp of the various FOT indices to correctly detect spirometric BHR were as follows: DRSRm: Se=91.3%, Sp=81.2%; DRSR10: Se=91.3%, Sp=95.8%; delta%Rm: Se=86.9%, Sp=52.1%; and delta%R10: Se=91.3%, Sp=58.3%. Dose-response slopes of indices of forced oscillation technique resistance, especially the dose-response slope of resistance at 10Hz are proposed as simple quantitative indices of bronchial responsiveness which can be calculated for all subjects and that may be useful in occupational epidemiology.

Sick-building symptoms in office workers in northeastern France: a pilot study.

STUDY OBJECTIVES: To verify that sick building symptoms are present in north-eastern France office workers; to try to identify new confounding factors. METHODS: The design was that of a cross-sectional study with control group. We studied with the same methods the personnel of an air-conditioned building (n=425), and of a naturally ventilated building (n=351). Air temperature and humidity, bacterial and fungal densities were measured by the same technical staff in the two buildings. A standard questionnaire on irritative and respiratory symptoms, personal and family history, and lifestyle was completed by the participants. RESULTS: In univariate analysis, exposure to air-conditioning was associated with an increased prevalence of symptoms (odds ratios-OR-between 1.54 and 2.84). A significant increase in sickness absence was also found among subjects working in air-conditioned offices. As a series of factors were suspected to interfere with these associations, logistic regression was applied. This method confirmed exposure to be an independent determinant of 7 symptoms, and also identified two determinants not previously described: a family history of respiratory diseases and "do-it-yourself' activities. IN CONCLUSION: we found the sick building symptoms to be present in a group of French office workers exposed to air-conditioning. We confirmed the influence of a number of confounding factors and described two further confounders - do-it-yourself activities at home and a history of familial respiratory disease.