•A multi-residue multi-families method for the analysis of 136 pharmaceuticals and hormones.•An innovative, rapid and simple sample extraction based on QuEChERS.•A method validated for the ...quantification, based on LC–TOF-MS instrument.•34 target substances detected in various sewage sludge.
The aim of this study was to develop an analytical method for the analysis of a wide range of hormonal steroids and pharmaceutical compounds in sewage sludge. Thus, 136 substances were selected, including 119 pharmaceuticals and 17 hormonal steroids. An innovative sample preparation procedure based on the quick, easy, cheap, effective, rugged and safe (QuEChERS) method was developed. The analysis was then performed using liquid chromatography coupled with time-of-flight mass spectrometry. This analytical procedure was validated by evaluating the specificity, quadratic curve fitting, recovery, reproducibility and limits of detection and quantification. The method allows the analysis of the majority of the target compounds with limits of detection ranging from 1ng/g to 2500ng/g, depending on the nature of the substance. The protocol was then successfully applied to various types of sludge (limed, digested, dried, liquid and composted) collected in several sewage works in France. Among the target compounds, 34 were quantified at levels up to 6000ng/g. Among the most commonly detected pharmaceuticals were the antiemetic domperidone (mean concentration 769ng/g) and the antiepileptic lamotrigine (mean concentration 31ng/g) whose presence had, to our knowledge, never been shown in sludge.
The aim of this study was to develop an analytical method for the analysis of a wide range of hormonal steroids and pharmaceutical compounds in sewage sludge. Thus, 136 substances were selected, ...including 119 pharmaceuticals and 17 hormonal steroids. An innovative sample preparation procedure based on the quick, easy, cheap, effective, rugged and safe (QuEChERS) method was developed. The analysis was then performed using liquid chromatography coupled with time-of-flight mass spectrometry. This analytical procedure was validated by evaluating the specificity, quadratic curve fitting, recovery, reproducibility and limits of detection and quantification. The method allows the analysis of the majority of the target compounds with limits of detection ranging from 1 ng/g to 2500 ng/g, depending on the nature of the substance. The protocol was then successfully applied to various types of sludge (limed, digested, dried, liquid and composted) collected in several sewage works in France. Among the target compounds, 34 were quantified at levels up to 6000 ng/g. Among the most commonly detected pharmaceuticals were the antiemetic domperidone (mean concentration 769 ng/g) and the antiepileptic lamotrigine (mean concentration 31 ng/g) whose presence had, to our knowledge, never been shown in sludge.
•Disease worsening is the principal reason for switching to fingolimod•Patient preferences enter into the decision in one-third of cases•Whatever the reason for switching, the improvement rate after ...switching is similar•Improved treatment acceptability is observed after switching to fingolimod
Timely treatment switching is an important strategy in optimising management of patients with relapsing remitting multiple sclerosis (RRMS). Patient preferences, as well as clinical benefit, may contribute to the switch decision. Information on reasons determining switching choices and on outcome according to the reason for switching is scarce. Study objectives were to describe the consequences of switching to fingolimod in terms of clinical improvement according to the reasons underlying the switch and to evaluate treatment acceptability from the patient's perspective.
This prospective observational study was conducted by 71 neurologists in France and included patients with RRMS switching to fingolimod following ≥6 months treatment with a first-line disease modifying treatment (DMT). Reasons for switching were documented. Patients were evaluated at inclusion and 12 months after initiating fingolimod. Physicians documented clinical status by relapse activity, disability (EDSS) at each visit and improvement with the Clinical Global Impression – Change (CGI-C) at Month 12. Patients rated improvement at Month 12 with the Patient Global Impression – Change (PGI-C) and treatment acceptability with the ACCEPT® questionnaire. Adverse events reported during fingolimod treatment were documented.
Overall 232 patients were recruited of whom 190 could be analysed. Multiple reasons for switching were frequently given; 113 patients (59.4%) switched from a first-line injectable DMT. Switching was motivated by disease worsening in 161 patients (84.7%), tolerability in 35 (18.4%) and patient preference in 58 (30.5%). During the follow-up period, 38 patients (20.0%) experienced at least one exacerbation. The mean EDSS score was stable (2.0 ± 1.3 at inclusion; 2.0 ± 1.5 at M12). With the CGI-C, 67 patients (38.7%) were considered improved and 23 (13.3%) worsened. Although no obvious differences in CGI-C ratings were observed as a function of the reason for switching, when patient preferences entered into the decision, the proportion of patients considered minimally improved was somewhat higher (37.7%) and the proportion considered unchanged somewhat lower (41.5%). With the PGI-C, more patients rated themselves improved than were rated as improved by the physician: of 64 patients rated as ‘no change’ on the CGI-C, 21 (32.8%) rated themselves as ‘improved’ and 10 (15.6%) as ‘worsened’. The overall level of agreement between the two measures was moderate (κ = 0.48 95% CI: 0.35 – 0.60). The mean general treatment acceptability score on the ACCEPT® questionnaire was 42.7 95%CI: 34.5 – 50.9 at inclusion (reflecting acceptability of the previous DMT) and 64.6 95%CI: 57.6 – 71.6 at M12 (reflecting acceptability of fingolimod). Mean dimension scores ranged from 36.7 for effectiveness to 72.2 for medication inconvenience at inclusion and from 63.4 for effectiveness to 96.8 for medication inconvenience at M12. The frequency and nature of reported adverse events was consistent with the well-characterised safety profile of fingolimod.
Most patients switching from a first DMT to fingolimod do so due to persistent disease activity during the initial treatment, although patient preferences are also important. Switching is followed by a reduction in disease activity, perceived improvement in the clinical state of the patient and improved acceptability of treatment.
