Infictieuze complicaties van biologicals bij de behandeling van reumatoïde artritis

De behandeling van reumatoïde artritis heeft een revolutie ondergaan sinds de introductie van biologicals. Een bekende complicatie van deze middelen is een verhoging van het risico op ernstige infecties, wat in verschillende mate bij de verschillende klassen voorkomt. Doordat TNF-alfaremmers onder andere granuloomvorming tegengaan, vormen ze een belangrijke risicofactor voor de reactivatie van latente tuberculose (tbc). Tocilizumab remt interleukine-6. Abatacept remt de T-celcostimulatie, waardoor een robuuste T-celrespons wordt tegengegaan. Rituximab, een monoclonaal dat CD20-positieve B-cellen depleteert, heeft als belangrijk risico reactivatie van hepatitis B-virus. Ook hepatitis C-virus- en JC-virusreactivatie zijn bij rituximab beschreven. Het risico op overige ernstige infecties lijkt bij alle biologicals ongeveer even hoog. Een bijzondere categorie zijn de Janus-kinase (JAK)-remmers, die zorgen voor een verminderde expressie van pro-inflammatoire genen. Van deze middelen is bekend dat ze waarschijnlijk een sterk verhoogd risico op herpes zoster geven. Onderzoek naar de invloed van deze middelen op het microbioom staat nog in de kinderschoenen: alleen van TNF-alfaremming is onderzocht wat dit doet op de darmkolonisatie

Infections in Biological and Targeted Synthetic Drug Use in Rheumatoid Arthritis:Where do We Stand? A Scoping Review and Meta-analysis

Introduction: The advent of biological and targeted synthetic therapies has revolutionized rheumatoid arthritis (RA) treatment. However, this has come at the price of an increased risk of infections. The aim of this study was to present an integrated overview of both serious and non-serious infections, and to identify potential predictors of infection risk in RA patients using biological or targeted synthetic drugs. Methods: We systematically reviewed available literature from PubMed and Cochrane and performed multivariate meta-analysis with meta-regression on the reported infections. Randomized controlled trials and prospective and retrospective observational studies including patient registry studies were analyzed, combined as well as separately. We excluded studies focusing on viral infections only. Results: Infections were not reported in a standardized manner. Meta-analysis showed significant heterogeneity that persisted after forming subgroups by study design and follow-up duration. Overall, the pooled proportions of patients experiencing an infection during a study were 0.30 (95% CI, 0.28–0.33) and 0.03 (95% CI, 0.028–0.035) for any kind of infections or serious infections only, respectively. We found no potential predictors that were consistent across all study subgroups. Conclusions: The high heterogeneity and the inconsistency of potential predictors between studies show that we do not yet have a complete picture of infection risk in RA patients using biological or targeted synthetic drugs. Besides, we found non-serious infections outnumbered serious infections by a factor 10:1, but only a few studies have focused on their occurrence. Future studies should apply a uniform method of infectious adverse event reporting and also focus on non-serious infections and their impact on treatment decisions and quality of life.</p

Assessment of dam trapping efficiency from water residence time: Application to fluvial sediment transport in the Adour, Dordogne, and Garonne River basins (France)

Dam-trapping efficiency can be estimated by using the hydraulic residence time. On the regional scale, the global impact of several dams can be assessed by taking into account the spatial organization of dams along the river network. Therefore, in this study, a method is proposed to estimate the global-trapping efficiency, TEw, for any watershed containing more than one dam. This method is applied to the Adour, Dordogne, and Garonne River watersheds (southwestern France). The spatial organization of dams and its impact on TEw and on sediment yields measured at 37 TSM sampling stations over 2 years are discussed. Positive correlation between drainage areas and river sediment loads corrected from dam regulation using TEw, as well as comparisons between TEw-corrected sediment yields and sediment yields measured upstream from dams, point out the interest of the method in order to reconstitute the natural sediment yields

Impact of motor fluctuations on real-life gait in Parkinson’s patients

Background people with PD (PWP) have an increased risk of becoming inactive. Wearable sensors can provide insights into daily physical activity and walking patterns. Research questions (1) is the severity of motor fluctuations associated with sensor-derived average daily walking quantity? (2) is the severity of motor fluctuations associated with the amount of change in sensor-derived walking quantity after levodopa intake? Methods 304 Dutch PWP from the Parkinson@Home study were included. At baseline, all participants received a clinical examination. During the follow-up period (median: 97 days; 25-Interquartile range-IQR: 91 days, 75-IQR: 188 days), participants used the Fox Wearable Companion app and streamed smartwatch accelerometer data to a cloud platform. The first research question was assessed by linear regression on the sensor-derived mean time spent walking/day with the severity of fluctuations (MDS-UPDRS item 4.4) as independent variable, controlled for age and MDS-UPDRS part-III score. The second research question was assessed by linear regression on the sensor-derived mean post-levodopa walking quantity, with the sensor-derived mean pre-levodopa walking quantity and severity of fluctuations as independent variables, controlled for mean time spent walking per day, age and MDS-UPDRS part-III score. Results PWP spent most time walking between 8am and 1pm, summing up to 72 ± 39 (mean ± standard deviation) minutes of walking/day. The severity of motor fluctuations did not influence the mean time spent walking (B = 2.4 ± 1.9, p = 0.20), but higher age (B = −1.3 ± 0.3, p = < 0.001) and greater severity of motor symptoms (B = −0.6 ± 0.2, p < 0.001) was associated with less time spent walking (F(3,216) = 14.6, p<.001, R2 =.17). The severity of fluctuations was not associated with the amount of change in time spent walking in relation to levodopa intake in any part of the day. Significance Analysis of sensor-derived gait quantity suggests that the severity of motor fluctuations is not associated with changes in real-life walking patterns in mildly to moderate affected PWP

Creating an Optimality Index – Netherlands: a validation study

Abstract Background At present, the maternity care system in the Netherlands is being reorganized into an integrated model of care, shifting the focus of midwives to include increasing numbers of births in hospital settings and clients with medium risk profiles. In light of these changes, it is useful for midwives to have a tool which may help them in reflecting upon care practices that promote physiological childbirth practices. The Optimality Index-US is an evidence based tool, designed to measure optimal perinatal care processes and outcomes. It has been validated for use in the United States (OI-US), United Kingdom (OI-UK) and Turkey (OI-TR). The objective of this study was to adapt the OI-US for the Dutch maternity care setting (OI-NL). Methods Translation and back translation were applied to create the OI-NL. A panel of maternity care experts (n = 10) provided input for face validation items in the OI-NL. Assessment of inter-rater reliability and ease of use was also conducted. Following this, the OI-NL was used prospectively to collect data on 266 women who commenced intrapartum care under the responsibility of a midwife. Twice groups were compared, based on parity and on care-setting at birth. Mean scores between these groups, corrected for perinatal background factors were assessed for discriminant validity. Results Face validity was established for OI-NL on the basis of expert input. Discriminant validity was confirmed by conducting multiple regressions analyses for parity (β = 6.21, P = 0.00) and for care-setting (β = 12.1, p = 0.00). Inter-rater reliability was 98%, with one item (Apgar score) sensitive to scoring differences. Conclusion OI-NL is a valid and reliable tool for use in the Dutch maternity care setting. In addition to its value for assessing evidence-based maternity care processes and outcomes, there is potential for use for learning and reflection. Against the backdrop of a changing maternity care system, and due to the specificity of its items OI-NL may be of value as a tool for detecting subtle changes indicative of escalating medicalization of childbirth in the Netherlands.https://deepblue.lib.umich.edu/bitstream/2027.42/143165/1/12884_2018_Article_1735.pd

Point-of-care therapeutic drug monitoring of tumour necrosis factor-α inhibitors using a single step immunoassay

Therapeutic drug monitoring (TDM) of tumor necrosis factor-α (TNFα)-inhibitors adalimumab and infliximab is important to establish optimal drug dose and maximize treatment efficacy. Currently, TDM is primarily performed with ELISA techniques in clinical laboratories, resulting in a long sample-to-result workflow. Point-of-care (POC) detection of these therapeutic antibodies could significantly decrease turnaround times and allow for user-friendly home-testing. Here, we adapted the recently developed bioluminescent dRAPPID (dimeric Ratiometric Plug-and-Play Immunodiagnostics) sensor platform to allow POC TDM of infliximab and adalimumab. We applied the two best performing dRAPPID sensors, with limit-of-detections of 1 pM and 17 pM, to measure the infliximab and adalimumab levels in 49 and 40 patient serum samples, respectively. The analytical performance of dRAPPID was benchmarked with commercial ELISAs and yielded Pearson's correlation coefficients of 0.93 and 0.94 for infliximab and adalimumab, respectively. Furthermore, a dedicated bioluminescence reader was fabricated and used as a readout device for the TDM dRAPPID sensors. Subsequently, infliximab and adalimumab patient serum samples were measured with the TDM dRAPPID sensors and bioluminescence reader, yielding Pearson's correlation coefficients of 0.97 and 0.86 for infliximab and adalimumab, respectively, and small proportional differences with ELISA (slope was 0.97 ± 0.09 and 0.96 ± 0.20, respectively). The adalimumab and infliximab dRAPPID sensors, in combination with the dedicated bioluminescence reader, allow for ease-of-use TDM with a fast turnaround time and show potential for POC TDM outside of clinical laboratories.</p

Point-of-care therapeutic drug monitoring of tumour necrosis factor-α inhibitors using a single step immunoassay

Therapeutic drug monitoring (TDM) of tumor necrosis factor-α (TNFα)-inhibitors adalimumab and infliximab is important to establish optimal drug dose and maximize treatment efficacy. Currently, TDM is primarily performed with ELISA techniques in clinical laboratories, resulting in a long sample-to-result workflow. Point-of-care (POC) detection of these therapeutic antibodies could significantly decrease turnaround times and allow for user-friendly home-testing. Here, we adapted the recently developed bioluminescent dRAPPID (dimeric Ratiometric Plug-and-Play Immunodiagnostics) sensor platform to allow POC TDM of infliximab and adalimumab. We applied the two best performing dRAPPID sensors, with limit-of-detections of 1 pM and 17 pM, to measure the infliximab and adalimumab levels in 49 and 40 patient serum samples, respectively. The analytical performance of dRAPPID was benchmarked with commercial ELISAs and yielded Pearson's correlation coefficients of 0.93 and 0.94 for infliximab and adalimumab, respectively. Furthermore, a dedicated bioluminescence reader was fabricated and used as a readout device for the TDM dRAPPID sensors. Subsequently, infliximab and adalimumab patient serum samples were measured with the TDM dRAPPID sensors and bioluminescence reader, yielding Pearson's correlation coefficients of 0.97 and 0.86 for infliximab and adalimumab, respectively, and small proportional differences with ELISA (slope was 0.97 ± 0.09 and 0.96 ± 0.20, respectively). The adalimumab and infliximab dRAPPID sensors, in combination with the dedicated bioluminescence reader, allow for ease-of-use TDM with a fast turnaround time and show potential for POC TDM outside of clinical laboratories.</p

Heavy metal distribution in some French forest soils: evidence for atmospheric contamination

This study is one of very few dealing with the distribution and the origin of heavy metals in French soils from a priori non-polluted forest areas. The abundance of heavy metals measured in these soils decreases as follows: Cr) Zn)Pb)Ni)Cu)Co4Cd. Total concentrations of Pb, Cr and Ni in some soils exceed the European thresholds for non-polluted soils and even the French association of normalization critical values for sludge spreading. The lowest heavy metal contents are observed in acid soils while the highest concentrations are in the calcaric cambisol and in the mollic andosol, which is rather scarce as compared with the other French forest soils. With the exception of the podzol, Cr and Ni concentrations increase with depth in all soil profiles. The distribution pattern of Co, Cu, Zn depends on the soil characteristics. In some acid soils, however, Cu and Zn decrease with depth. Pb and Cd are accumulated in the upper soil horizons. Heavy metals accumulate in deep soil horizons in relation to important clay content in the dystric planosol and stagnic luvisol. The concentration of each heavy metal is always controlled by different parameters (soil pH, iron and aluminum oxide content, clay content, organic matter and cation exchange capacity), which are heavy metal specific. This study highlights the metal-trapping character of andosol and calcaric soil, the weak heavy metal retention in acid soils, the leaching and trapping character in leached clayed soils, and the migration of heavy metals in the podzol. Pb and Cr concentrations indicate a significant enrichment in surface horizons from various soils in areas which receive significant acid atmospheric pollution. Particularly, the highest Pb content is observed in a soil located in the N-NE part of France. Lead isotope ratios measured in the cambic podzol and the calcaric cambisol, exhibit the importance of the anthropogenic sources and particularly the influence of global atmospheric inputs from leaded gasoline compared to regional and local industrial emissions. The anthropogenic Pb contribution is estimated to 83, 30 and 11%, respectively, for surface, intermediate and deep horizons of the cambic podzol located in the northern part of France, and to 68% in surface horizon of the calcaric cambisol located in the Alps

Patterns of Recurrence and Survival After Pelvic Treatment for Locally Advanced Penile Cancer

BACKGROUND: Penile cancer (PeCa) is rare, and the survival of patients with advanced disease remains poor. A better understanding of where treatment fails could aid the development of new treatment strategies. OBJECTIVE: To describe the disease course after pelvic lymph node (LN) treatment for PeCa. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analysed 228 patients who underwent pelvic LN treatment with curative intent from 1969 to 2016. The main treatment modalities were neoadjuvant chemotherapy, chemoradiation, and pelvic LN dissection. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In the case of multiple recurrence locations, the most distant location was taken and recorded as follows: local (penis), regional (inguinal and pelvic LN), and distant (any other location). A competing risk analysis was used to calculate the time to recurrence per location, and a Kaplan-Meier analysis was used for overall survival (OS). RESULTS AND LIMITATIONS: The median follow-up of the surviving patients was 79 mo. The reason for pelvic treatment was pelvic involvement on imaging (29%), two or more tumour-positive inguinal LNs (61%), or inguinal extranodal extension (52%). More than half of the patients (61%) developed a recurrence. The median recurrence-free survival was 11 mo. The distribution was local in 9%, regional in 27%, and distant in 64% of patients. The infield control rate of nonsystemically treated patients was 61% (113/184). From the start of pelvic treatment, the median OS was 17 mo (95% confidence interval 12–22). After regional or distant recurrence, all but one patient died of PeCa with median OS after a recurrence of 4.4 (regional) and 3.1 (distant) mo. This study is limited by its retrospective nature. CONCLUSIONS: The prognosis of PeCa patients treated on their pelvis who recur despite locoregional treatment is poor. The tendency for systemic spread emphasises the need for more effective systemic treatment strategies. PATIENT SUMMARY: In this report, we looked at the outcomes of penile cancer patients in an expert centre undergoing various treatments on their pelvis. We found that survival is poor after recurrence despite locoregional treatment. Therefore, better systemic treatments are necessary