The gout epidemic in French Polynesia: a modelling study of data from the Ma'i u'u epidemiological survey.

BACKGROUND: Gout is the most common cause of inflammatory arthritis worldwide, particularly in Pacific regions. We aimed to establish the prevalence of gout and hyperuricaemia in French Polynesia, their associations with dietary habits, their comorbidities, the prevalence of the HLA-B*58:01 allele, and current management of the disease. METHODS: The Ma'i u'u survey was epidemiological, prospective, cross-sectional, and gout-focused and included a random sample of adults from the general adult population of French Polynesia. It was conducted and data were collected between April 13 and Aug 16, 2021. Participants were randomly selected to represent the general adult population of French Polynesia on the basis of housing data collected during the 2017 territorial census. Each selected household was visited by a research nurse from the Ma'i u'u survey who collected data via guided, 1-h interviews with participants. In each household, the participant was the individual older than 18 years with the closest upcoming birthday. To estimate the frequency of HLA-B*58:01, we estimated HLA-B haplotypes on individuals who had whole-genome sequencing to approximately 5× average coverage (mid-pass sequencing). A subset of individuals who self-reported Polynesian ancestry and not European, Chinese, or other ancestry were used to estimate Polynesian-ancestry specific allele frequencies. Bivariate associations were reported for weighted participants; effect sizes were estimated through the odds ratio (OR) of the association calculated on the basis of a logistic model fitted with weighted observations. FINDINGS: Among the random sample of 2000 households, 896 participants were included, 140 individuals declined, and 964 households could not be contacted. 22 participants could not be weighted due to missing data, so the final weighted analysis included 874 participants (449 [51·4%] were female and 425 [48·6%] were male) representing the 196 630 adults living in French Polynesia. The estimated prevalence of gout was 14·5% (95% CI 9·9-19·2), representing 28 561 French Polynesian adults, that is 25·5% (18·2-32·8) of male individuals and 3·5% (1·0-6·0) of female individuals. The prevalence of hyperuricaemia was estimated at 71·6% (66·7-76·6), representing 128 687 French Polynesian adults. In multivariable analysis, age (OR 1·5, 95% CI 1·2-1·8 per year), male sex (10·3, 1·8-60·7), serum urate (1·6, 1·3-2·0 per 1 mg/dL), uraturia (0·8, 0·8-0·8 per 100 mg/L), type 2 diabetes (2·1, 1·4-3·1), BMI more than 30 kg/m2 (1·1, 1·0-1·2 per unit), and percentage of visceral fat (1·7, 1·1-2·7 per 1% increase) were associated with gout. There were seven heterozygous HLA-B*58:01 carriers in the full cohort of 833 individuals (seven [0·4%] of 1666 total alleles) and two heterozygous carriers in a subset of 696 individuals of Polynesian ancestry (two [0·1%]). INTERPRETATION: French Polynesia has an estimated high prevalence of gout and hyperuricaemia, with gout affecting almost 15% of adults. Territorial measures that focus on increasing access to effective urate-lowering therapies are warranted to control this major public health problem. FUNDING: Variant Bio, the French Polynesian Health Administration, Lille Catholic University Hospitals, French Society of Rheumatology, and Novartis.

Relationship between immunosuppression and intensive care unit-acquired colonization and infection related to multidrug-resistant bacteria: a prospective multicenter cohort study.

PURPOSE: The impact of immunosuppression on intensive care unit (ICU)-acquired colonization and infection related to multidrug-resistant (MDR) bacteria (ICU-MDR-col and ICU-MDR-inf, respectively) is unknown. METHODS: We carried out an observational prospective cohort study in 8 ICUs in France (all with single-bed rooms and similar organizational characteristics). All consecutive patients with an ICU stay > 48 h were included, regardless of immune status, and followed for 28 days. Patients underwent systematic screening for colonization with MDR bacteria upon admission and every week subsequently. Immunosuppression was defined as active cancer or hematologic malignancy, neutropenia, solid-organ transplant, use of steroids or immunosuppressive drugs, human immunodeficiency virus infection and genetic. The primary endpoint was the incidence rate of a composite outcome including ICU-MDR-col and/or ICU-MDR-inf. RESULTS: 750 patients (65.9% males, median age 65 years) were included, among whom 264 (35.2%) were immunocompromised. Reasons for ICU admission, severity scores and exposure to invasive devices and antibiotics during ICU stay were comparable between groups. After adjustment for center and pre-specified baseline confounders, immunocompromised patients had a lower incidence rate of ICU-MDR-col and/or ICU-MDR-inf (adjusted incidence ratio 0.68, 95% CI 0.52-0.91). When considered separately, the difference was significant for ICU-MDR-col, but not for ICU-MDR-inf. The distribution of MDR bacteria was comparable between groups, with a majority of Enterobacteriacae resistant to third-generation cephalosporins (~ 74%). CONCLUSION: Immunocompromised patients had a significantly lower incidence rate of a composite outcome including ICU-MDR-col and/or ICU-MDR-inf. This finding points to the role of contact precautions and isolation measures, and could have important implications on antibiotic stewardship in this population.

Mapping and Crosswalk of the Oxford Hip Score and Different Versions of the Hip Disability and Osteoarthritis Outcome Score.

BACKGROUND: Patient-reported outcome measures such as the Oxford-12 Hip Score and Hip Disability and Osteoarthritis Outcome Score (HOOS) are used in daily orthopaedic practice to evaluate patients. Because different studies use different scores, it would be important to build conversion tables between scores (crosswalk) to compare the results of one study with those of another study. Various mapping methods can be used to develop crosswalk tables that convert Oxford-12 scores to the HOOS (and its derivatives, including the HOOS physical function short form, HOOS joint replacement, and HOOS-12) and vice versa. Although prior studies have investigated this issue, they are limited to short forms of the HOOS score. Consequently, they cannot be applied to hip preservation surgery and do not include quality-of-life items, whereas the Oxford-12 Hip Score is used for all hip evaluations. QUESTIONS/PURPOSES: We prospectively studied the Oxford-12 and HOOS and its derivatives to (1) determine which version of the HOOS has the best mapping with the Oxford-12, (2) define the most-appropriate mapping method using selected indicators, and (3) generate crosswalk tables between these two patient-reported outcome measures. METHODS: The study enrolled 500 adult patients before primary THA (59% men [294 of 500 patients]) with hip osteoarthritis or avascular necrosis of the femoral head who completed the HOOS and Oxford-12. Patients were recruited from January 2018 to September 2019 in a tertiary-care university hospital, and we included all primary THAs in patients older than 18 years with a BMI lower than 35 kg/m2 and greater than 18 kg/m2. After a minimum of 6 months of follow-up, 39% (195 of 500) of the patients were assessed using the same tools. To determine which version of the HOOS mapped best to the Oxford-12 and what the most-appropriate mapping method was, we used preoperative data from all 500 patients. Because there is no consensus on the method to establish crosswalk, various mapping methods (linear regression, tobit regression, and quantile regression) and equating methods (linear equating and equipercentile method) were applied along with cross-validation to determine which method was the most suitable and which form of the HOOS provided the best result according to different criteria (mean absolute error, r2, and Kolmogorov-Smirnov distance).To generate crosswalk tables, we created a conversion table (between the Oxford-12 and the HOOS form that was chosen after answering our first research question and the method chosen after answering our second question) using preoperative and postoperative data (n = 695). This table was meant to be simple to use and allows easy conversions from one scoring system to another. RESULTS: The Oxford-12 and HOOS were strongly correlated (Pearson correlation coefficient range 0.586-0.842) for the HOOS subcategories and HOOS physical function, HOOS joint replacement, and HOOS-12. The correlation between the HOOS-12 and Oxford-12 was the strongest (r = 0.825). According to the three different criteria and five methods, the HOOS-12 was the best suited for mapping. The goal was to minimize the mean absolute error (perfect model = 0), have a Kolmogorov-Smirnov distance as close as possible to 0, and have the r2 as close as possible to 1. Regarding the most-suitable method for the crosswalk mapping (research question 2), the five methods generated similar results for the r2 (range 0.63-0.67) and mean absolute error (range 6-6.2). For the Kolmogorov-Smirnov distance, the equipercentile method was the best (Kolmogorov-Smirnov distance 0.04), with distance reduced by 43% relative to the regression methods (Kolmogorov-Smirnov distance 0.07). A graphical comparison of the predicted and observed scores showed that the equipercentile method provided perfect superposition of predicted and observed values after mapping. Finally, crosswalk tables were produced between the HOOS-12 and Oxford-12. CONCLUSION: The HOOS-12 is the most complete and suitable form of the HOOS for mapping with the Oxford-12, while the equipercentile method is the most suitable for predicting values after mapping. This study provides clinicians with a reliable tool to crosswalk between these scores not only for joint arthroplasty but also for all types of hip surgeries while also assessing quality of life. Our findings should be confirmed in additional studies. CLINICAL RELEVANCE: The resulting crosswalk tables can be used in meta-analyses, systematic reviews, or clinical practice to compare clinical studies that did not include both outcome scores. In addition, with these tools, the clinician can collect only one score while still being able to compare his or her results with those obtained in other databases and registries, and to add his or her results to other databases and joint registries.

Can the minimal clinically important difference be determined in a French-speaking population with primary hip replacement using one PROM item and the Anchor strategy?

BACKGROUND: The impact of surgery on the patient is classically assessed on pre- and post-treatment scores. However, it is increasingly recommended to rank these results according to the minimal clinically important difference (MCID), using either the data distribution method or the anchor method, latter consisting in an extra question specifically targeting the patient's improvement. MCIDs vary between populations and, to the best of our knowledge; there have been no investigations in France regarding this in the context of total hip replacement (THR). Therefore, we conducted a prospective study in a population with THR to determine: 1) whether MCID scores in France were comparable to those reported in the data from the international literature; 2) whether a general item taken from a different score could serve as an anchor; and 3) whether an item from the actual questionnaire itself could serve as an anchor. HYPOTHESIS: When pre- and post-treatment scores are available, an item from the questionnaire itself can serve as an anchor for MCID. MATERIAL AND METHODS: In a prospective observational study, 123 primary THR patients (69 male, 54 female), out of 150 initially included, completed the 5 domains of the HOOS hip disability and osteoarthritis outcome score and the Oxford-12 questionnaire, preoperatively and at 6-12 months. The MCID was calculated via the distribution-based and the anchor-based methods. Two Oxford items (questions 1 and 2) and 2 HOOS items (questions S1 and Q4) were used as anchors, as well as a supplementary question on improvement and the Forgotten Joint Score (FJS). RESULTS: At a mean 10.12±1.2 months' follow-up [range, 6.5-11.9 months], the Oxford-12 score increased from 19±8 [3-35] to 40±10 [8-48] (p<0.001), all HOOS components demonstrated improvement, and the FJS at the final follow-up was 71±29 [0-100]. The general items (Oxford question 1 and HOOS question Q4) were more discriminating than the joint-specific items (Oxford question 2 and HOOS question S1). Based on results from the 3 anchors (improvement rated 1 to 5, Oxford question 1 and HOOS question Q4), 3 to 5 patients showed deterioration, 5 to 6 were unchanged, 30 to 40 were slightly improved, and 73 to 80 were improved by THR. The mean MCID on both distribution and anchor methods was 9 [5.5-12] for Oxford-12, 20 [12-27] for HOOS symptoms, 26 [10-36] for HOOS pain, 22 [11.5-28] for HOOS function, 26 [13-34] for HOOS sport and 22 [14-28] for HOOS quality of life. DISCUSSION: The MCID for the Oxford-12 and HOOS scores in a French population was comparable to data from the past literature. Using a score item as an anchor to define improvement is possible, but only if a general item is used. LEVEL OF EVIDENCE: IV; prospective study without control group. CLINICAL TRIALS REGISTRATION: NCT04057651.

Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus.

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG's antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.

Does change in language change the properties of a shortened score previously validated in its complete version? Validation of the French versions of the HOOS-12 and KOOS-12 scores in primary knee and hip arthroplasties.

BACKGROUND: The HOOS and KOOS scoring questionnaires comprise respectively 40 and 42 items; a shorter 12-item version was recently developed, but remains to be validated in a French-speaking population. We therefore conducted a prospective study: 1) to determine whether the new 12-item versions in French are equivalent to the longer HOOS and KOOS versions, and 2) to validate the French-language HOOS-12 and KOOS-12 patient-reported outcome measures in a population of primary total hip and knee arthroplasty: validity, reliability, and responsiveness. HYPOTHESIS: The change in language in a score already validated in its long version does not alter its properties in the short version. MATERIAL AND METHODS: One hundred patients (59 males, 41 females) undergoing primary total hip arthroplasty and 100 patients (43 males, 57 females) undergoing primary total knee arthroplasty were prospectively included. They filled out the original HOOS or KOOS questionnaires, their simplified versions (PS: Physical function Short form; JR: Joint Replacement) and the short HOOS-12 and KOOS-12 versions, and also the Oxford-12 score assessing the affected joint, preoperatively, then at 6-12 months. RESULTS: The 100% response rate confirmed ease of use. There were no redundant items. There were strong correlations between the 12-item and longer versions (>0.9). The HOOS-12 and KOOS-12 scores were reliable and valid: 1) there were no ceiling or floor effects for pre- or postoperative KOOS-12 scores, although a ceiling effect was found for HOOS-12 postoperatively (20% of patients having maximum scores of 100); 2) internal consistency was confirmed, with Cronbach alpha>0.8; 3) external consistency between Oxford-12 and HOOS-12/KOOS-12 was excellent, with Pearson correlation coefficient>0.8. Sensitivity to pre-/postoperative change was confirmed, with effect size>0.8. DISCUSSION: The present study confirmed the usefulness of this new 12-item form for HOOS and KOOS. Properties were identical between the French- and English-language versions, authorising everyday use of these simpler versions. LEVEL OF EVIDENCE: IV; prospective study without control group.

Association between anticholinergic burden and hospital readmission in older patients: a prospective analysis.

OBJECTIVE: Despite known adverse effects of anticholinergic (AC) medication, little work has been devoted to the impact of high anticholinergic burden on the rate of hospital readmission. The purpose of this study was to analyze prospectively the link between high AC burden and the rate of all-cause thirty-day hospital readmission in older people. STUDY DESIGN: This was a prospective non-interventional study conducted from January to August 2019 in one acute-care geriatric ward. All hospital stays of patients aged at least 75 years who were discharged to their home were included in the analysis. AC burden was determined from discharge prescriptions using the Anticholinergic Drug Scale (ADS) and the Anticholinergic Risk Scale (ARS), and defined as high if ≥3. RESULTS: The analysis concerned 350 hospital stays. Median patient age was 88 years (interquartile interval 84-91). In a multivariate analysis, the risk of hospital readmission within 30 days was not increased for patients with high AC burden (ADS≥3): odds ratio 1.16 [95% confidence interval 0.56-2.37], compared to a patient whose anticholinergic burden was not high. CONCLUSION: Unlike retrospective studies on this issue, the findings of our prospective analysis do not support a higher risk of hospital admission within 30 days for older people with high AC burden as assessed from their discharge prescriptions.

Arterial Pulsatility and Circulating von Willebrand Factor in Patients on Mechanical Circulatory Support.

BACKGROUND: The main risk factor for bleeding in patients with continuous-flow mechanical circulatory support (CF-MCS) is the acquired von Willebrand factor (VWF) defect related to the high shear-stress forces developed by these devices. Although a higher bleeding rate has been reported in CF-MCS recipients who had reduced pulsatility, the relation between pulsatility and the VWF defect has never been studied. OBJECTIVES: The purpose of this study was to investigate the relation between pulsatility and VWF under CF-MCS. METHODS: We assessed the effect of 2 CF-MCS on VWF multimer degradation in a mock circulatory loop (model 1). Using these devices, we investigated in a dose-effect model (model 2) 3 levels of pulsatility in 3 groups of swine. In a cross-over model (model 3), we studied the effects of sequential changes of pulsatility on VWF. We reported the evolution of VWF multimerization in a patient undergoing serial CF-MCS and/or pulsatile-MCS. RESULTS: We demonstrated the proteolytic degradation of VWF multimers by high shear CF-MCS in a circulatory loop without pulsatility. We observed both in swine models and in a patient that the magnitude of the VWF degradation is modulated by the pulsatility level in the high shear-stress level condition, and that the restoration of pulsatility is a trigger for the endothelial release of VWF. CONCLUSIONS: We demonstrated that the VWF defect reflects the balance between degradation induced by the shear stress and the endothelial release of new VWF triggered by the pulsatility. This modulation of VWF levels could explain the relationship between pulsatility and bleeding observed in CF-MCS recipients. Preservation of pulsatility may be a new target to improve clinical outcomes of patients.

How to Compare the Length of Stay of Two Samples of Inpatients? A Simulation Study to Compare Type I and Type II Errors of 12 Statistical Tests.

BACKGROUND: Although many researchers in the field of health economics and quality of care compare the length of stay (LOS) in two inpatient samples, they often fail to check whether the sample meets the assumptions made by their chosen statistical test. In fact, LOS data show a highly right-skewed, discrete distribution in which most of the observations are tied; this violates the assumptions of most statistical tests. OBJECTIVES: To estimate the type I and type II errors associated with the application of 12 different statistical tests to a series of LOS samples. METHODS: The LOS distribution was extracted from an exhaustive French national database of inpatient stays. The type I error was estimated using 19 sample sizes and 1,000,000 simulations per sample. The type II error was estimated in three alternative scenarios. For each test, the type I and type II errors were plotted as a function of the sample size. RESULTS: Gamma regression with log link, the log rank test, median regression, Poisson regression, and Weibull survival analysis presented an unacceptably high type I error. In contrast, the Student standard t test, linear regression with log link, and the Cox models had an acceptable type I error but low power. CONCLUSIONS: When comparing the LOS for two balanced inpatient samples, the Student t test with logarithmic or rank transformation, the Wilcoxon test, and the Kruskal-Wallis test are the only methods with an acceptable type I error and high power.

Is Reperfusion Useful in Ischaemic Stroke Patients Presenting with a Low National Institutes of Health Stroke Scale and a Proximal Large Vessel Occlusion of the Anterior Circulation?

BACKGROUND: In population-based studies, patients presenting with minor or mild stroke symptoms represent about two-thirds of stroke patients, and almost one-third of these patients are unable to ambulate independently at the time of discharge. Although mechanical thrombectomy (MT) has become the standard of care for acute ischaemic stroke with proximal large vessel occlusion (LVO) in the anterior circulation, the management of patients harbouring proximal occlusion and minor-to-mild stroke symptoms has not yet been determined by recent trials. The purpose of this study was to evaluate the impact of reperfusion on clinical outcome in low National Institutes of Health Stroke Scale (NIHSS) patients treated with MT. METHODS: We analysed 138 consecutive patients with acute LVO of the anterior circulation (middle cerebral artery M1 or M2 segment, internal carotid artery or tandem occlusion) with NIHSS <8, having undergone MT in 3 different centres. Reperfusion was graded using the modified thrombolysis in cerebral infarction (TICI) score and 3 grades were defined, ranging from failed or poor reperfusion (TICI 0, 1, 2A) to complete reperfusion (TICI 3). The primary clinical endpoint was an excellent outcome defined as a modified Rankin score (mRs) 0-1 at 3-months. The impact of reperfusion grade was assessed in univariate and multivariate analyses. The secondary endpoints included favourable functional outcome (90-day mRS 0-2), death and safety concerns. RESULTS: Successful reperfusion was achieved in 81.2% of patients (TICI 2B, n = 47; TICI 3, n = 65). Excellent outcome (mRs 0-1) was achieved in 69 patients (65.0%) and favourable outcome (mRs ≤2) in 108 (78.3%). Death occurred in 7 (5.1%). Excellent outcome increased with reperfusion grades, with a rate of 34.6% in patients with failed/poor reperfusion, 61.7% in patients with TICI 2B reperfusion, and 78.5% in patients with TICI 3 reperfusion (p < 0.001). In multivariate analysis adjusted for patient characteristics associated with excellent outcome, the reperfusion grade remained significantly associated with an increase in excellent outcome; the OR (95% CI) was 3.09 (1.06-9.03) for TICI 2B and 6.66 (2.27-19.48) for TICI 3, using the failed/poor reperfusion grade as reference. Similar results were found regarding favourable outcome (90-day mRs 0-2) or overall mRS distribution (shift analysis). CONCLUSION: Successful reperfusion is strongly associated with better functional outcome among patients with proximal LVO in the anterior circulation and minor-to-mild stroke symptoms. Randomized controlled studies are mandatory to assess the benefit of MT compared with optimal medical management in this subset of patients.

Successful Reperfusion With Mechanical Thrombectomy Is Associated With Reduced Disability and Mortality in Patients With Pretreatment Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score ≤6.

BACKGROUND AND PURPOSE: In acute ischemic stroke patients, diffusion-weighted imaging (DWI)-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is correlated with infarct volume and is an independent factor of functional outcome. Patients with pretreatment DWI-ASPECTS ≤6 were excluded or under-represented in the recent randomized mechanical thrombectomy trials. Our aim was to assess the impact of reperfusion in pretreatment DWI-ASPECTS ≤6 patients treated with mechanical thrombectomy. METHODS: We analyzed data collected between January 2012 and August 2015 in a bicentric prospective clinical registry of consecutive acute ischemic stroke patients treated with mechanical thrombectomy. Every patient with a documented internal carotid artery or middle cerebral artery occlusion with pretreatment DWI-ASPECTS ≤6 was eligible for this study. The primary end point was a favorable outcome defined by a modified Rankin Scale score ≤2 at 90 days. RESULTS: Two hundred and eighteen patients with a DWI-ASPECTS ≤6 were included. Among them, 145 (66%) patients had successful reperfusion at the end of mechanical thrombectomy. Reperfused patients had an increased rate of favorable outcome (38.7% versus 17.4%; P=0.002) and a decreased rate of mortality at 3 months (22.5% versus 39.1%; P=0.013) compared with nonreperfused patients. The symptomatic intracranial hemorrhage rate was not different between the 2 groups (13.0% versus 14.1%; P=0.83). However, in patients with DWI-ASPECTS <5, favorable outcome was low (13.0% versus 9.5%; P=0.68) with a high mortality rate (45.7% versus 57.1%; P=0.38) with or without successful reperfusion. CONCLUSIONS: Successful reperfusion is associated with reduced mortality and disability in patients with a pretreatment DWI-ASPECTS ≤6. Further data from randomized studies are needed, particularly in patients with DWI-ASPECTS <5.

Incidence and Predictive Factors of Postprandial Hyperinsulinemic Hypoglycemia After Roux-en-Y Gastric Bypass: A Five year Longitudinal Study.

BACKGROUND: Postprandial hyperinsulinemic hypoglycemia (PHH) is often reported after Roux-en-Y gastric bypass (RYGB). In the absence of a prospective study, the clinical and biological determinants of PHH remain unclear. OBJECTIVE: To determine the incidence and predictive factors of PHH after RYGB. METHODS: Participants were 957 RYGB patients enrolled in an ongoing longitudinal cohort study. We analyzed the results of an oral glucose tolerance test (OGTT) routinely performed before surgery and 1 and/or 5 years after. PHH was defined as blood glucose < 50 mg/dL AND plasma insulin > 3 mU/L at 120 minutes post glucose challenge. Validated indices of insulin sensitivity (Matsuda index), beta-cell function (Insulinogenic index), and beta-cell mass (fasting C-peptide: glucose ratio) were calculated, from glucose, insulin, and c-peptide values measured during OGTT. RESULTS: OGTT results were available in all patients at baseline, in 85.6% at 12 months and 52.8% at 60 months. The incidence of PHH was 0.5% at baseline, 9.1% * and 7.9%* at 12 months and 60 months following RYGB (*: P < 0.001). In multivariate logistic regression analysis, PHH after RYGB was independently associated with lower age (P = 0.005), greater weight loss (P = 0.031), as well as higher beta-cell function (P = 0.002) and insulin sensitivity (P < 0.001), but not with beta-cell mass (P = 0.381). A preoperative elevated beta-cell function was an independent predictor of PHH after RYGB (receiver operating characteristics curve area under the curve 0.68, P = 0.04). CONCLUSIONS:: The incidence of PHH significantly increased after RYGB but remained stable between 1 and 5 years. The estimation of beta-cell function with an OGTT before surgery can identify patients at risk for developing PHH after RYGB.

Characteristics of Patients with Alcohol Dependence Seeking Baclofen Treatment in France: A Two-Centre Comparative Cohort Study.

AIM: To characterize the profile of patients seeking baclofen treatment for alcohol dependence in France. METHOD: We compared retrospectively baclofen seekers and baclofen non-seekers within a cohort of consecutive outpatients with alcohol dependence who attended a first appointment for alcohol treatment at two French addiction centres between September 2012 and March 2014. We documented socio-demographic characteristics; comorbid psychiatric, addiction, alcohol dependence features; patients' initial drinking goal, and referral status; and treatment retention at 6 and 12 months. RESULTS: Of the 289 patients identified, 107 were baclofen seekers and 182 were baclofen non-seekers. The only parameters significantly associated with baclofen seekers in multivariate analyses were a greater baseline alcohol consumption (ß = 15.4, 95% CI: 0.18-30.65, P = 0.05), a controlled-drinking initial goal (OR = 14.9, 95% CI: 7.7-29, P < 0.0001) and self-referral (OR = 6.6, 95% CI: 3.7-12, P < 0.0001), baclofen seekers being eight times more likely to be self-referred and treatment-naïve (OR = 8.8, 95% CI: 4.1-18.9, P < 0.0001). Baclofen seekers were more likely to be retained in treatment at 6 months (OR = 3.5, 95% CI: 1.8-6.7, P < 0.0001) and 12 months (OR = 1.9, 95% CI: 1.1-3.2, P = 0.019). CONCLUSION: In France, the perspective of controlled drinking offered by baclofen treatment may have attracted more self-referred patients, including those without previous alcohol treatment, to attend treatment, than the usual treatment options. These findings raise the question as to whether future public health strategies on alcohol should more prominently promote some aspects of alcohol treatment, such as patient's preference and treatment options, in order to reduce the treatment gap in alcohol dependence.

Evidence of IL-17, IP-10, and IL-10 involvement in multiple-organ dysfunction and IL-17 pathway in acute renal failure associated to Plasmodium falciparum malaria.

BACKGROUND: Plasmodium falciparum malaria in India is characterized by high rates of severe disease, with multiple organ dysfunction (MOD)-mainly associated with acute renal failure (ARF)-and increased mortality. The objective of this study is to identify cytokine signatures differentiating severe malaria patients with MOD, cerebral malaria (CM), and cerebral malaria with MOD (CM-MOD) in India. We have previously shown that two cytokines clusters differentiated CM from mild malaria in Maharashtra. Hence, we also aimed to determine if these cytokines could discriminate malaria subphenotypes in Odisha. METHODS: P. falciparum malaria patients from the SCB Medical College Cuttack in the Odisha state in India were enrolled along with three sets of controls: healthy individuals, patients with sepsis and encephalitis (n = 222). We determined plasma concentrations of pro- and anti-inflammatory cytokines and chemokines for all individuals using a multiplex assay. We then used an ensemble of statistical analytical methods to ascertain whether particular sets of cytokines/chemokines were predictors of severity or signatures of a disease category. RESULTS: Of the 26 cytokines/chemokines tested, 19 increased significantly during malaria and clearly distinguished malaria patients from controls, as well as sepsis and encephalitis patients. High amounts of IL-17, IP-10, and IL-10 predicted MOD, decreased IL-17 and MIP-1α segregated CM-MOD from MOD, and increased IL-12p40 differentiated CM from CM-MOD. Most severe malaria patients with ARF exhibited high levels of IL-17. CONCLUSION: We report distinct differences in cytokine production correlating with malarial disease severity in Odisha and Maharashtra populations in India. We show that CM, CM-MOD and MOD are clearly distinct malaria-associated pathologies. High amounts of IL-17, IP-10, and IL-10 were predictors of MOD; decreased IL-17 and MIP-1α separated CM-MOD from MOD; and increased IL-12p40 differentiated CM from CM-MOD. Data also suggest that the IL-17 pathway may contribute to malaria pathogenesis via different regulatory mechanisms and may represent an interesting target to mitigate the pathological processes in malaria-associated ARF.

Detection of adverse drug events detection: data aggregation and data mining.

Adverse drug events (ADEs) are a public health issue. The objective of this work is to data-mine electronic health records in order to automatically identify ADEs and generate alert rules to prevent those ADEs. The first step of data-mining is to transform native and complex data into a set of binary variables that can be used as causes and effects. The second step is to identify cause-to-effect relationships using statistical methods. After mining 10,500 hospitalizations from Denmark and France, we automatically obtain 250 rules, 75 have been validated till now. The article details the data aggregation and an example of decision tree that allows finding several rules in the field of vitamin K antagonists.

Data-mining-based detection of adverse drug events.

Every year adverse drug events (ADEs) are known to be responsible for 98,000 deaths in the USA. Classical methods rely on report statements, expert knowledge, and staff operated record review. One of our objectives, in the PSIP project framework, is to use data mining (e.g., decision trees) to electronically identify situations leading to risk of ADEs. 10,500 hospitalization records from Denmark and France were used. 500 rules were automatically obtained, which are currently being validated by experts. A decision support system to prevent ADEs is then to be developed. The article examines a decision tree and the rules in the field of vitamin K antagonists.

PASE: a web-based platform for peptide/protein microarray experiments.

Peptide microarray technology requires bioinformatics and statistical tools to manage, store, and analyze the large amount of data produced. To address these needs, we developed a system called protein array software environment (PASE) that provides an integrated framework to manage and analyze microarray information from polypeptide chip technologies.

Tools for statistical analysis with missing data: application to a large medical database.

Missing data is a common feature of large data sets in general and medical data sets in particular. Depending on the goal of statistical analysis, various techniques can be used to tackle this problem. Imputation methods consist in substituting the missing values with plausible or predicted values so that the completed data can then be analysed with any chosen data mining procedure. In this work, we study imputation in the context of multivariate data and we evaluate a number of methods which can be used by today's standard statistical software packages. Imputation using multivariate classification, multiple imputation and imputation by factorial analysis are compared using simulated data and a large medical database (from the diabetes field) with numerous missing values. Our main result is to provide a control chart for assessing data quality after the imputation process. To this end, we developed an algorithm for which the input is a set of parameters describing the underlying data (e.g., covariance matrix, distribution) and the output is a chart which plots the change in the prediction error with respect to the proportion of missing values. The chart is built by means of an iterative algorithm involving four steps: (1) a sample of simulated data is drawn by using the input parameters; (2) missing values are randomly generated; (3) an imputation method is used to fill in the missing data and (4) the prediction error is computed. Steps 1 to 4 are repeated in order to estimate the distribution of the prediction error. The control chart was established for the 3 imputation methods studied here, assuming a multivariate normal distribution of data. The use of this tool on a large medical database was then investigated. We show how the control chart can be used to assess the quality of the imputation process in the pre-processing step upstream of data mining procedures.