[Interest of a geostatistical approach to analyze the geographical disparities in human papillomavirus vaccine coverage in France]. / Intérêt d'une approche géostatistique pour analyser les disparités géographiques de la couverture vaccinale contre les papillomavirus humains en France.

BACKGROUND: The use of geostatistical methods remains rare in health studies. In order to assess the usefulness of the geostatistical approach in epidemiology, we chose to apply these methods to the vaccination coverage rate (VCR) against human papillomavirus (HPV) in France. Indeed, HPV vaccine coverage remains low in France and geographical disparities are sizable. The objective of this study was to identify the socioecological factors that may explain these geographical variations. METHODS: Sociological, economic and behavioral data for 2016 have been gathered (demographics and public health database, web and social networks) and were correlated with the HPV VCR vaccine coverage over the French territory. Homogeneous geographical areas defined by strong correlations for groups of variables were selected. In each homogeneous area, principal component analysis was performed and a geostatistical approach provided an estimate predicting vaccine coverage at a given scale. RESULTS: HPV VCR spatial variations in France cannot be fully explained by a single model. In urban areas, a low rate of HPV VCR is preferentially associated with unfavorable socioeconomic factors (poverty, unemployment, immigration). In rural areas, HPV VCR is preferentially associated with sociocultural factors (socio-professional categories, education level, interest in alternative medicines the anti-vaccine movement). Two secondary geographical areas were defined: the Île-de-France region and 12 departments in northeastern France. In the Île-de-France region, the association with the economic factors one again appears as in urban areas in general. The northeasteran departments represent a particular case insofar as HPV VCR is relatively high, notwithstanding economic poverty indicators. CONCLUSION: Geostatistical modeling successfully identifies new potential explanations for HPV VCR geographical disparities in France. These results could help to adapt or develop future vaccination programs in specific areas by taking into account the sociological, economic and behavioral characteristics of their populations.

Long-term outcome of liver transplantation in childhood: A study of 20-year survivors.

We report the results of a study of survival, liver and kidney functions, and growth with a median follow-up of 24 years following liver transplantation in childhood. From 1988 to 1993, 128 children underwent deceased donor liver transplantation (median age: 2.5 years). Twenty-year patient and graft survival rates were 79% and 64%, respectively. Raised serum aminotransferase and/or γ-glutamyl transferase activities were present in 42% of survivors after a single transplantation. Graft histology (35 patients) showed signs of chronic rejection in 11 and biliary obstruction in 5. Mean total fibrosis scores were 4.5/9 and 3/9 in patients with abnormal and normal serum liver tests, respectively. Glomerular filtration rate was <90 mL·min-1 in 35 survivors, including 4 in end-stage renal disease who were undergoing dialysis or had undergone renal transplantation. Median final heights were 159 cm for women and 172 cm for men; final height was below the target height in 37 patients. Twenty-year survival after childhood liver transplantation may be close to 80%, and final height is within the normal range for most patients. However, chronic kidney disease or altered liver biochemistries are present in over one third of patients, which is a matter of concern for the future.

Pazopanib or placebo in completely resected stage I NSCLC patients: results of the phase II IFCT-0703 trial.

BACKGROUND: Adjuvant treatment in resected stage I non-small-cell lung cancer (NSCLC) is generally not recommended. Pazopanib is an oral tyrosine kinase inhibitor of VEGFR-1/2/3 and PDGFR-α/ß. We explored the feasibility and efficacy of adjuvant pazopanib in this population. PATIENTS AND METHODS: In this double-blind phase II/III trial, patients with resected stage I NSCLC were randomized to placebo or pazopanib 800 mg/day (P800) for 6 months with a two-step Fleming design. The primary endpoint was compliance (percentage of patients receiving ≥3 months pazopanib). From the interim analysis after 64 patients were included, the IDMC recommended reducing to pazopanib 400 mg/day (P400) due to insufficient compliance, with a one-step Fleming. Although unplanned, survival data were analyzed. RESULTS: A total of 71 patients were enrolled in each arm; 61% were male, 91% were smokers, median age was 60 years, 80% had pathological stage IA, and 16% had squamous cell carcinoma. Pazopanib compliance was 38% [95% confidence interval (CI) 23-55] with P800, increasing to 69% (95% CI 50-84; P = 0.027) with P400. Two patients had grade 4 toxicities with P800. The most common grade 3 toxicities were increased transaminases (16%), hypertension (13%), and diarrhea (9%) with P800, and gastrointestinal disorders (16%; 6% diarrhea) and hypertension (6%) with P400. Median follow-up was 47 months. Three-year recurrence-free survival was 76% (95% CI 65%-86%) with pazopanib and 83% (95% CI 74%-92%) with placebo [hazard ratio = 1.3 (95% CI 0.6-2.7), P = 0.53]. Five-year overall survival was 83% (95% CI 72-94) with pazopanib and 94% [95% CI 88-100] with placebo [hazard ratio = 1.8 (95% CI 0.6-5.5), P = 0.26]. CONCLUSIONS: In resected stage I NSCLC patients adjuvant 400 mg/day pazopanib but not 800 mg/day was feasible, although possibly infra-therapeutic and failed to improve relapse-free survival.

Changes in movement organization and control strategies when learning a biomechanically constrained gait pattern, racewalking: a PCA study.

Combining advances from gait analysis and motor learning fields, this study aims to examine invariant characteristics and practice-related changes in the control of walking gait when learning a biomechanically constrained pattern, racewalking (RW). RW's regulation imposes a straightened knee at the stance phase which differentiates it qualitatively from normal walking. Using 3D motion analysis, we computed key kinematic variables from a whole-body model. Principal component analysis was then used as a tool to evaluate the evolution of normal walking synergies (S0) immediately at the first practice session (S1) and further with practice (S1-S4). Before the start of practice, normal walking was characterized by two predominant control dimensions explaining an upper-extremities/antero-posterior component (PC1) and a lower-extremities/vertical component (PC2). Compared to normal walking, the immediate increase at S1 in the number of PCs needed to explain a significant portion of movement variance could be suggestive of a recruitment of a task-specific component. With practice, the significant decrease in the variance accounted for by PC1 and in the correlations between many variables could indicate a destabilization of spontaneous tendencies to facilitate the adoption of more task-specific coordinative pattern. PC2 seemed to be reinforced with practice where a significant increase in its explained variance was observed. In sum, this study shows that common features in the gait control are preserved with practice, and the movement reorganization, however, seems rather defined by shifts in the relative contribution of some variables within each PC.

Influence of histological subtypes on the risk of an invasive recurrence in a large series of stage I borderline ovarian tumor including 191 conservative treatments.

BACKGROUND: The overall prognosis of stage I borderline ovarian tumors (BOT) is excellent but a small percentage of patients die to their disease. The prognostic factors for such a rare event are still not clearly defined. The aim of this study was to determine these factors for recurrence per se and recurrence in the form of invasive carcinoma in a large series of stage I tumors. METHODS: A retrospective review of patients with BOT. Three inclusion criteria were defined: (i) a centralized histological review; (ii) macroscopic stage I tumors; (iii) exclusion of metastatic disease to the ovaries. RESULTS: From 2000 to 2010, 254 patients fulfilled inclusion criteria [140 had mucinous BOT (MBOT) and 114 a serous BOT (SBOT)], and 191 had undergone conservative management. After a median follow-up of 45 months, 43 patients had developed recurrences (31 borderline and 12 invasive). The risks of recurrences were statistically increased after conservative treatment, particularly after a cystectomy, in patients with stage IB and among patients with incompletely staged tumors. In the subgroup of conservatively treated patients (representing 75% of our population), the risks of recurrences were statistically increased in patients affected by a SBOT, in patients who had undergone a cystectomy, in patients with stage IB disease and in patients with a micropapillary pattern (MPP). MBOT and the presence of a MPP were identified as prognostic factors for invasive disease. CONCLUSIONS: In the present series of BOT with the largest number of patients treated conservatively to date, the presence of a MPP and the mucinous subtype were associated with a higher rate of progression to carcinoma after conservative management. These important results suggest that MBOT belong to a 'high-risk' group likely to develop an invasive recurrence after fertility-sparing surgery in stage I BOT.

Learning an energy-demanding and biomechanically constrained motor skill, racewalking: movement reorganization and contribution of metabolic efficiency and sensory information.

This study investigated how novices learn an energy demanding and biomechanically constrained task like racewalking. The first aim was to examine if movement reorganizes according to some fundamental strategies, proceeding in different stages (Newell, 1985). The second aim was to investigate the link between movement reorganization, metabolic efficiency and perceived exertion. Seven participants undertook seven racewalking learning sessions on a motorized treadmill, with increased velocity as the experiment progressed, in order to reach a goal performance speed of 10 kmh(-1). Peripheral/central perceived exertion ratings, kinematic and metabolic data were collected during the 1st, 4th, 6th and 7th session. Repeated-measures (Learning Session×Speed) ANOVAs on kinematic data showed a proximal-to-distal directional trend in movement reorganization, with significant practice-related changes in pattern coordination and decreased variability. Early movement reorganization occurred at the 1st session ("coordination stage") and progressed until the 4th session ("control stage") to reach a plateau. In contrast, metabolic efficiency and peripheral perceived exertion continued optimizing until the last session, probably occurring in concurrence with the control stage. Peripheral perceived exertion presented the highest correlation with the global movement reorganization variables suggesting that it could play a key role in guiding movement reorganization in the learning process, improving efficiency as a result.