This phase 1–phase 2a study of the use of low-dose interleukin-2 to treat vasculitis associated with HCV infection suggests the presence of a therapeutic effect that is mediated by an increase in ...regulatory T cells.
Interleukin-2 has been identified for its capacity to stimulate T cells in vitro
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and has been used to boost effector immune responses in patients with cancers and infectious diseases.
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,
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It is a registered indication when used as an adjunct for the treatment of renal-cell carcinoma, but there is a response to treatment in less than 10% of those with the disease, a finding partly explained by the discovery that interleukin-2 mediates the survival and suppressive function of regulatory T cells (Tregs),
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which are known to suppress antitumor effector responses.
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,
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A marked increase in levels of Tregs has been . . .
The 36-Item Short Form Health Survey (SF-36) is a popular questionnaire for measuring the self-perception of quality of life in a given population of interest. Processing the answers of a participant ...comprises the calculation of 10 scores corresponding to 8 scales measuring several aspects of perceived health and 2 summary components (physical and mental). Surprisingly, no study has compared score values issued from a telephone interview versus those from an internet-based questionnaire self-completion.
This study aims to compare the SF-36 score values issued from a telephone interview versus those from an internet-based questionnaire self-completion.
Patients with an internet connection and returning home after hospital discharge were enrolled in the SENTIPAT multicenter randomized trial on the day of discharge. They were randomized to either self-completing a set of questionnaires using a dedicated website (internet group) or providing answers to the same questionnaires administered during a telephone interview (telephone group). This ancillary study of the trial compared SF-36 data related to the posthospitalization period in these 2 groups. To anticipate the potential unbalanced characteristics of the responders in the 2 groups, the impact of the mode of administration of the questionnaire on score differences was investigated using a matched sample of individuals originating from the internet and telephone groups (1:1 ratio), in which the matching procedure was based on a propensity score approach. SF-36 scores observed in the internet and telephone groups were compared using the Wilcoxon-Mann-Whitney test, and the score differences between the 2 groups were also examined according to Cohen effect size.
Overall, 29.2% (245/840) and 75% (630/840) of SF-36 questionnaires were completed in the internet and telephone groups, respectively (P<.001). Globally, the score differences between groups before matching were similar to those observed in the matched sample. Mean scores observed in the telephone group were all above the corresponding values observed in the internet group. After matching, score differences in 6 out of the 8 SF-36 scales were statistically significant, with a mean difference greater than 5 for 4 scales and an associated mild effect size ranging from 0.22 to 0.29, and with a mean difference near this threshold for 2 other scales (4.57 and 4.56) and a low corresponding effect size (0.18 and 0.16, respectively).
The telephone mode of administration of SF-36 involved an interviewer effect, increasing SF-36 scores. Questionnaire self-completion via the internet should be preferred, and surveys combining various administration methods should be avoided.
ClinicalTrials.gov NCT01769261; https://www.clinicaltrials.gov/ct2/show/record/NCT01769261.
Summary Background Reports of an increased risk of lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease are controversial. We assessed this risk in a ...prospective observational cohort study. Methods 19 486 patients with inflammatory bowel disease, of whom 11 759 (60·3%) had Crohn's disease and 7727 (39·7%) had ulcerative colitis or unclassified inflammatory bowel disease, were enrolled in a nationwide French cohort by 680 gastroenterologists, who reported details of immunosuppressive therapy during the observation period, cases of cancer, and deaths. The risk of lymphoproliferative disorder was assessed according to thiopurine exposure. Median follow-up was 35 months (IQR 29–40). Findings At baseline, 5867 (30·1%) of patients were receiving, 2809 (14·4%) had discontinued, and 10 810 (55·5%) had never received thiopurines. 23 new cases of lymphoproliferative disorder were diagnosed, consisting of one case of Hodgkin's lymphoma and 22 cases of non-Hodgkin lymphoproliferative disorder. The incidence rates of lymphoproliferative disorder were 0·90 per 1000 (95% CI 0·50–1·49) patient-years in those receiving, 0·20/1000 (0·02–0·72) patient-years in those who had discontinued, and 0·26/1000 (0·10–0·57) patient-years in those who had never received thiopurines (p=0·0054). The multivariate-adjusted hazard ratio of lymphoproliferative disorder between patients receiving thiopurines and those who had never received the drugs was 5·28 (2·01–13·9, p=0·0007). Most cases associated with thiopurine exposure matched the pathological range of post-transplant disease. Interpretation Patients receiving thiopurines for inflammatory bowel disease have an increased risk of developing lymphoproliferative disorders. Funding Programme Hospitalier de Recherche Clinique National ( AOM05157 ), Association François Aupetit, Délégation Inter-régionale de la Recherche clinique Ile de France-Assistance Publique Hôpitaux de Paris (AP-HP), Ligue contre le Cancer, and Fonds de Recherche de la Société Nationale Française de Gastro-entérologie.
Using serum samples routinely collected in 9144 adults from a French general population-based cohort, we identified 353 participants with a positive anti-SARS-CoV-2 IgG test, among whom 13 were ...sampled between November 2019 and January 2020 and were confirmed by neutralizing antibodies testing. Investigations in 11 of these participants revealed experience of symptoms possibly related to a SARS-CoV-2 infection or situations at risk of potential SARS-CoV-2 exposure. This suggests early circulation of SARS-CoV-2 in Europe.
The dynamics of viral shedding and symptoms following influenza virus infection are key factors when considering epidemic control measures. The authors reviewed published studies describing the ...course of influenza virus infection in placebo-treated and untreated volunteers challenged with wild-type influenza virus. A total of 56 different studies with 1,280 healthy participants were considered. Viral shedding increased sharply between 0.5 and 1 day after challenge and consistently peaked on day 2. The duration of viral shedding averaged over 375 participants was 4.80 days (95% confidence interval: 4.31, 5.29). The frequency of symptomatic infection was 66.9% (95% confidence interval: 58.3, 74.5). Fever was observed in 37.0% of A/H1N1, 40.6% of A/H3N2 (p = 0.86), and 7.5% of B infections (p = 0.001). The total symptoms scores increased on day 1 and peaked on day 3. Systemic symptoms peaked on day 2. No such data exist for children or elderly subjects, but epidemiologic studies suggest that the natural history might differ. The present analysis confirms prior expert opinion on the duration of viral shedding or the frequency of asymptomatic influenza infection, extends prior knowledge on the dynamics of viral shedding and symptoms, and provides original results on the frequency of respiratory symptoms or fever.
ObjectiveMagnitude and independent drivers of the risk of acute arterial events in IBD are still unclear. We addressed this question in patients with IBD compared with the general population at a ...nationwide level.DesignUsing the French National Hospital Discharge Database from 2008 to 2013, all patients aged 15 years or older and diagnosed with IBD were identified and followed up until 31 December 2013. The rates of incident acute arterial events were calculated and the impact of time with active disease (period around hospitalisation for IBD flare or IBD-related surgery) on the risk was assessed by Cox regression adjusted for traditional cardiovascular risk factors.ResultsAmong 210 162 individuals with IBD (Crohn’s disease (CD), n=97 708; UC, n=112 454), 5554 incident acute arterial events were identified. Both patients with CD and UC had a statistically significant overall increased risk of acute arterial events (standardised incidence ratio (SIR) 1.35; 95% CI 1.30 to 1.41 and SIR 1.10; 95 CI 1.06 to 1.13, respectively). The highest risk was observed in patients under the age of 55 years, both in CD and UC. The 3-month periods before and after IBD-related hospitalisation were associated with an increased risk of acute arterial events in both CD and UC (HR 1.74; 95 CI 1.44 to 2.09 and 1.87; 95% CI 1.58 to 2.22, respectively).ConclusionPatients with IBD are at increased risk of acute arterial events, with the highest risk in young patients. Disease activity may also have an independent impact on the risk.
Several studies have shown a relatively high mortality rate among young people infected by the 2009 pandemic influenza A (H1N1) virus. Here we compared the age distributions of morbidity and ...mortality during two seasonal influenza epidemics (H1N1 and H3N2) in France and the United States with those of the 2009 H1N1 pandemic waves in the same countries.
Age-standardized ratios were used to compare the age distribution of morbidity and mortality due to influenza between the two countries and across the different years. Non parametric analysis of variance was used to compare these ratios between epidemic and pandemic influenza.
Age distribution of morbidity was similar between the 2009 pandemic and seasonal epidemics due to H1N1 (p = 0.72) and H3N2 viruses (p = 0.68). In contrast, the proportion of under-60s among influenza deaths was markedly higher during the 2009 pandemic (peak <20 years) than during the seasonal epidemics (respectively p = 0.007 and p = 0.0008).
Young age was a principal mortality risk factor due to the 2009 H1N1 pandemic.
Abstract
Background
The risk of mortality in intensive care units (ICUs) is currently addressed by the implementation of scores using admission data. Their performances are satisfactory when ...complications occur early after admission; however, they may become irrelevant in the case of long hospital stays. In this study, we developed predictive models of short-term mortality in the ICU from longitudinal data.
Methods
Using data collected throughout patients’ stays of at least 48 h from the MIMIC-III database, several statistical learning approaches were compared, including deep neural networks and penalized regression. Missing data were handled using complete-case analysis or multiple imputation.
Results
Complete-case analyses from 19 predictors showed good discrimination (AUC > 0.77 for several approaches) to predict death between 12 and 24 h onward, yet excluded 75% of patients from the initial target cohort, as data was missing for some of the predictors. Multiple imputation allowed us to include 70 predictors and keep 95% of patients, with similar performances.
Conclusion
This proof-of-concept study supports that automated analysis of electronic health records can be of great interest throughout patients’ stays as a surveillance tool. Although this framework relies on a large set of predictors, it is robust to data imputation and may be effective early after admission, when data are still scarce.
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