Background: Evidence is growing regarding the ability of platelet-rich plasma (PRP) injections to enhance functional capacity and alleviate pain in knee osteoarthritis (OA). However, heterogeneity in common practice regarding PRP preparation and biological content makes the initiation of this activity in a hospital complex. The aim of this study was to document the efficacy of a single PRP injection to treat knee OA and validate a routine care procedure. Methods: Fifty-seven patients with symptomatic knee OA received a single injection of large volume of very pure PRP. They were assessed at baseline and after one, three and six months, by measuring Knee Injury and Osteoarthritis Score (KOOS), Observed Pain after a 50-foot walk test and Visual Analog Scale (VAS) assessments. Magnetic Resonance Imaging (MRI) analysis was performed at baseline and six months after the procedure. The objective was to recover 50% of responders three months after the procedure using OMERACT-OARSI criteria. Results: A single administration of high volume pure PRP provided significant clinical benefit for 84.2% of the responders, three months after the procedure. The KOOS total score significantly increased from 43.5 ± 14.3 to 66.4 ± 21.7 six months after the procedure (p < 0.001). Pain also significantly decreased from 37.5 ± 25.1 to 12.9 ± 20.9 (p < 0.001). No difference was observed on MRI parameters. Conclusion: A single injection of large volume of very pure PRP is associated with significant functional improvement and pain relief, allowing initiation of daily PRP injection within our hospital.

In cancer epidemiology using population-based data, regression models for the excess mortality hazard is a useful method to estimate cancer survival and to describe the association between prognosis factors and excess mortality. This method requires expected mortality rates from general population life tables: each cancer patient is assigned an expected (background) mortality rate obtained from the life tables, typically at least according to their age and sex, from the population they belong to. However, those life tables may be insufficiently stratified, as some characteristics such as deprivation, ethnicity, and comorbidities, are not available in the life tables for a number of countries. This may affect the background mortality rate allocated to each patient, and it has been shown that not including relevant information for assigning an expected mortality rate to each patient induces a bias in the estimation of the regression parameters of the excess hazard model. We propose two parametric corrections in excess hazard regression models, including a single-parameter or a random effect (frailty), to account for possible mismatches in the life table and thus misspecification of the background mortality rate. In an extensive simulation study, the good statistical performance of the proposed approach is demonstrated, and we illustrate their use on real population-based data of lung cancer patients. We present conditions and limitations of these methods, and provide some recommendations for their use in practice.

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The aim of this study was to evaluate the recurrence rate of lithiasis following minimally invasive surgery to identify risk factors and mechanisms for recurrence of salivary gland lithiasis. Study Design: Retrospective case series. Methods: A retrospective study was conducted including all patients treated for salivary gland lithiasis by minimally invasive surgery, such as sialendoscopy, intracorporeal lithotripsy, extracorporeal lithotripsy, transoral approach, and combined approach in our Department. We analyzed the recurrence rate of salivary lithiasis, their topography and timeline. Result: Three hundred four patients were included in this study, the mean age was 49 years (range 12-90 years), and the mean duration of follow-up was 19.8 months (range 0-66 months). Fifteen patients (5%) presented secondary lithiasis. In all but one case, recurrences involved the same gland as primary lithiasis, and most frequently the submandibular gland. Recurrences occurred from 3 to 46 months postoperatively. Fourteen patients, who presented recurrence, had been initially treated by transoral approach. Recurrent lithiasis were treated by transoral approach or submandibulectomy. Conclusion: Salivary gland lithiasis recurrence was rare after minimally invasive salivary gland surgery. This study reinforced the concept that salivary gland lithiasis should be considered as a duct pathology.

Spatial cluster detection is a classical question in epidemiology: Are cases located near other cases? In order to classify a study area into zones of different risks and determine their boundaries, we have developed a spatial partitioning method based on oblique decision trees, which is called spatial oblique decision tree (SpODT). This non-parametric method is based on the classification and regression tree (CART) approach introduced by Leo Breiman. Applied to epidemiological spatial data, the algorithm recursively searches among the coordinates for a threshold or a boundary between zones, so that the risks estimated in these zones are as different as possible. While the CART algorithm leads to rectangular zones, providing perpendicular splits of longitudes and latitudes, the SpODT algorithm provides oblique splitting of the study area, which is more appropriate and accurate for spatial epidemiology. Oblique decision trees can be considered as non-parametric regression models. Beyond the basic function, we have developed a set of functions that enable extended analyses of spatial data, providing: inference, graphical representations, spatio-temporal analysis, adjustments on covariates, spatial weighted partition, and the gathering of similar adjacent final classes. In this paper, we propose a new R package, SPODT, which provides an extensible set of functions for partitioning spatial and spatiotemporal data. The implementation and extensions of the algorithm are described. Function usage examples are proposed, looking for clustering malaria episodes in Bandiagara, Mali, and samples showing three different cluster shapes.

Small clinical trials are trials in which the number of patients does not enable the objective of the study to be appropriately met with the usual methodological rules. This situation is common in the case of rare diseases, in paediatrics, in certain cancer pathologies or when the number of patients exposed to the treatment needs to be limited. The principal methodological problems are initially identified, and the classical methods (controlled, randomised, double-blind trial using parallel groups, crossover trial, factorial design, trial performed with several measures repeated over time, add-on design, randomised withdrawal design or early-escape design) and more uncommon methods (sequential approaches, meta-analyses, the 'N of 1' method and other methods that facilitate decision making or modelling) are then discussed. Subsequently, recommendations are made to ensure that the results obtained are not a matter of chance, and to increase the level of proof. Keywords: small trials, statistical methods, level of proof Small clinical trials are trials conducted and analysed using patient numbers lower than is required to meet the aims of the study according to the more common methodological rules. This paper therefore does not concern the standard phase I and II trials where the number of patients included in the study, although quantitatively small, is methodologically adapted to the aims of the study. It concerns all trials that aim to establish the proof of whether any given effect, be it of efficacy or tolerance, is present. PHARMACOLOGIE CLINIQUEThis situation is often the case with rare diseases, in paediatrics or in cancer treatment, when the external limitations of patient availability do not enable the recruitment of patient numbers that meet the usual assessment criteria. It is also the case when the number of patients exposed to the investigational treatment methods needs to be limited, either because of constraints regarding the particular protection of individuals (children, pregnant women), or because of the toxicity of the product (cancer treatment), or even its lack of efficacy (placebo, weak doses). The methodological issue in 'proof of concept' studies, the results of which lead to the decision on whether or not to continue developing a molecule, although based on a different context, can be related to this field.The main issue surrounding these small trials is the level of proof provided by the results of these studies, which reflects the relevance of using non-standard methods.Conducting a small trial through necessity reveals various levels of difficulties, some of which are not entirely specific to small trials, but are increased because of the reduced patient numbers. These include the following:1. The risk of not reaching a conclusion, even though there is a real difference between the therapeutic regimens being compared, because of the great variability in random fluctuations. Only a quantitatively important effect is likely to be given prominence.2. The caution necessary when extr...

Relative survival methods used to estimate the excess mortality of cancer patients rely on the background (or expected) mortality derived from general population life tables. These methods are based on splitting the observed mortality into the excess mortality and the background mortality. By assuming a regression model for the excess mortality, usually a Cox-type model, one may investigate the effects of certain covariates on the excess mortality. Some covariates are cancer-specific whereas others are variables that may influence the background mortality as well. The latter should be taken into account in the background mortality to avoid biases in estimating their effects on the excess mortality. Unfortunately, the available life table might not include such variables and, consequently, might provide inaccurate values of the background mortality. We propose a model that uses multiplicative parameters to correct potentially inaccurate background mortality. The model can be seen as an extension of the frequently used Estève model because we assume a Cox-type model for the excess mortality with a piecewise constant baseline function and introduce additional parameters that multiply the background mortality. The original and the extended model are compared, first in a simulation study, then in an application to colon cancer registry data.

Background Long-term growth in HIV-infected infants treated early in resource-limited settings is poorly documented. Incidence of growth retardation, instantaneous risk of death related to malnutrition and growth parameters evolution during the first five years of life of uninfected and early treated HIV-infected children were compared and associated factors with growth retardation were identified. Methods Weight-for-age (WAZ), weight-for-length (WLZ), and length-for-age (LAZ) Z-scores were calculated. The ANRS-PEDIACAM cohort includes four groups of infants with three enrolled during the first week of life: HIV-infected (HI, n = 69), HIV-exposed uninfected (HEU, n = 205) and HIV-unexposed uninfected (HUU, n = 196). The last group included HIV-infected infants diagnosed before 7 months of age (HIL, n = 141). The multi-state Markov model was used to describe the incidence of growth retardation and identified associated factors. Results During the first 5 years, 27.5% of children experienced underweight (WAZ<-2), 60.4% stunting (LAZ<-2) and 41.1% wasting (WLZ<-2) at least once. The instantaneous risk of death observed from underweight state (35.3 [14.1–88.2], 84.0 [25.5–276.3], and 6.0 [1.5–24.1] per 1000 person-months for 0–6 months, 6–12 months, and 12–60 months respectively) was higher than from non-underweight state (9.6 [5.7–16.1], 20.1 [10.3–39.4] and 0.3 [0.1–0.9] per 1000 person-months). Compared to HEU, HIL and HI children were most at risk of wasting (adjusted HR (aHR) = 4.3 (95%CI: 1.9–9.8), P<0.001 and aHR = 3.3 (95%CI: 1.4–7.9), P = 0.01 respectively) and stunting for HIL (aHR = 8.4 (95%CI: 2.4–29.7). The risk of underweight was higher in HEU compared to HUU children (aHR = 5.0 (CI: 1.4–10.0), P = 0.001). Others associated factors to growth retardation were chronic pathologies, small size at birth, diarrhea and CD4< 25%. Conclusions HIV-infected children remained at high risk of wasting and stunting within the first 5 years period of follow-up. There is a need of identifying suitable nutritional support and best ways to integrate it with cART in pediatric HIV infection global care.