Background: SinceMarch 1, 2017, medical cannabis (MC) can be prescribed nationwide in Germany. To date, there have been a number of qualitatively different studies on the effectiveness of MC in fibromyalgia syndrome (FMS). Objective: The aim of the studywas to investigate the effectiveness of THC in the course of interdisciplinary multimodal pain therapy (IMPT) on pain and several psychometric variables. Materials and methods: For the study, in the period 2017-2018, all patients in the pain ward of a clinic who were suffering from FMS and were treated in a multimodal interdisciplinary setting were selected based on inclusion criteria. The patients were examined separately according to groups with and without THC about pain intensity, various psychometric parameters and analgesic consumption during the stay. Results: Of the 120 FMS patients included in the study, 62 patients (51.7%) were treated with THC. In the parameters of pain intensity, depression, and quality of life, there was a significant improvement in the entire group during the stay (p < 0.001), which was significantly greater through the use of THC. In five of the seven analgesic groups examined, the dose was reduced or the drug discontinued significantly more often in the patients treated with THC. Conclusion: The results provide indications that THC can be considered as a medical alternative in addition to the substances previously recommended in various guidelines.

Objective: The objective of this study was to assess the potential value of patient-reported outcomes (PROs) of depression, fibromyalgia symptoms, and pain in predicting non-inflammatory vs. inflammatory diagnoses in rheumatology patients. Methods: This retrospective, single-center study evaluated electronic health record (EHR) data from adults who were seen for their first rheumatology consultation and subsequently received a diagnosis of an inflammatory (e.g., rheumatoid arthritis or spondyloarthritis) or non-inflammatory (e.g., osteoarthritis or fibromyalgia) condition. The PROs evaluated included depressive symptoms (Patient Health Questionnaire-2 [PHQ-2]), fibromyalgia symptom severity (FM SS), and pain. Results: A total of 3669 patients were evaluated, including patients with (n = 984; 26.82%) and without (n = 2685; 73.18%) inflammatory rheumatologic disease, of whom 141 (3.8%) had fibromyalgia. The non-inflammatory subgroup reported higher FM SS scores, and the inflammatory subgroup had higher pain and inflammatory markers. Bivariate models based on PHQ-2 and FM SS had a very low specificity (0.3%) for predicting non-inflammatory conditions, resulting in the misclassification of >99% of inflammatory cases. Adding pain, inflammatory markers, and other relevant EHR variables increased specificity but still resulted in a high level of misclassification. Conclusions: The PROs evaluated in this study are not suitable for predicting non-inflammatory vs. inflammatory rheumatologic disease, even when combined with other EHR variables.

Objectives: To assess tolerability of COVID-19 vaccination in patients with RA and controls based on patient-reported outcomes (PROs). Methods: In total, 266 study participants were included at 6 +/- 1 weeks after their second vaccination (BioNTech/Pfizer (72.2%), AstraZeneca (18.8%) and Moderna (9.0%)). In a cross-sectional, observational study design, PRO data were recorded regarding both total and symptom-level tolerability. Results: Overall tolerability was very high according to the patients' self-assessment scores (1.71 for the first and 1.72 for the second vaccination, 6-point Likert scale [1 (very good) to 6 (very poor)]) and did not differ significantly between patients with RA (n = 204) and controls (n = 62). Self-rated overall tolerability regarding first vaccination was significantly better (P = 0.002) in patients receiving mRNA vaccines (n = 193, mean tolerability 1.59) as compared with vector-vaccinated patients (n = 73, mean tolerability 2.04). Homologous or heterologous vaccination regimens had no statistically significant effect on vaccine tolerability (P = 0.131). Reservations about the vaccination were rare (6.4% for the first and 6.0% for the second vaccination) but significantly associated with poorer overall tolerability (P < 0.001) and significantly reduced willingness to recommend vaccination to others (P < 0.001 for the first and P = 0.004 for the second vaccination). Conclusion: Based on these real-world data, tolerability of COVID-19 vaccination was very good in both RA patients and controls. Reservations against COVID-19 vaccination were rare overall, but if present, associated with a significantly worse tolerability and a significantly lower degree of recommendation.

Ziel dieses Beitrags ist es, aufzuzeigen, wie patientenberichtete Ergebnisse („patient reported outcomes“ [PRO]) und patientenberichtete Erfahrungen („patient reported experiences“ [PRE]) einen wichtigen Beitrag zur Art und Weise der Diabetesversorgung, zur besseren Einbindung von Betroffenen in diese und zur Zusammenarbeit zwischen Fachkräften des Gesundheitswesens und Diabetespatienten leisten können. Diese Übersicht konzentriert sich auf die Definition und Messung von PRO und PRE, deren Bedeutung für eine personenzentrierte Diabetesversorgung und die Einbeziehung der Perspektive der Patienten in die Bewertung medizinischer, psychologischer und technologischer Interventionen. Zunehmend werden PRO von Herstellern, Zulassungsbehörden und der Politik als relevante Informationen für die Bewertung von Medikamenten, Technologien und der Diabetesversorgung akzeptiert. Ebenso können sie zur Qualitätssicherung und vergleichenden Bewertung Letzterer eingesetzt werden. Abschließend werden in der Übersichtsarbeit ungelöste Probleme im Zusammenhang mit PRO und PRE dargestellt. Diese betreffen die mangelnde Vergleichbarkeit der verwendeten Erhebungsinstrumente, die oft zu geringe Änderungssensitivität der zur Erfassung von Verbesserungen oder Verschlechterungen verwendeten Fragebogen sowie den fehlenden Konsens darüber, welche Änderung als klinisch relevant anzusehen ist.

Inactivated vaccines, such as tick-borne-encephalitis-virus-(TBEV) vaccine, have been discussed as less immunogenic in elderly and in immunocompromised patients. In this controlled cross-sectional cohort study, the antibody and cellular responses after TBEV-vaccination were investigated in 36 rheumatoid arthritis (RA) patients and 112 healthy controls (HC) by evaluating IgG-anti-TBEV concentration, neutralization and relative avidity index (RAI). Cellular reactivity was assessed by IFNgamma-producing spot-forming-units (SFU) by ELISPOT assay and flow cytometry. RA patients showed lower IgG-anti-TBEV compared to HC, which were influenced by age at and time since last TBEV vaccination and disease duration. High-responders regarding cellular immunity and avidity were less frequent in RA compared to HC. RA patients who had received booster vaccinations were more likely to demonstrate higher IgG-anti-TBEV responses compared to those who had not. In conclusion, RA patients showed a negative effect of age on anti-TBEV-IgG and immunological benefits of timely booster vaccination are suggested.

Objective:Several studies on the immunogenicity of vaccination against coronavirus disease 2019 (COVID-19) in patients with immune-mediated inflammatory diseases have evaluated the influence of DMARDs. The aim of the work presented here was to compare the humoral vaccine response after two vaccinations between patients with RA undergoing TNF inhibitor therapy and healthy controls. Methods:We assessed the humoral immune response, as measured by titres of neutralizing antibodies against the S1 antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in patients with RA and anti-TNF treatment vs. controls without immunomodulatory medication. One hundred and seven fully vaccinated individuals were included at 6 ± 1 weeks after the second vaccination [BioNTech/Pfizer (72.9%), AstraZeneca (17.8%) and Moderna (9.3%)]. Immune responses in terms of antibody titres were compared between both subgroups with (n = 45) and without (n = 62) exposure to anti-TNF medication. The comparison was performed as a cross-sectional, single-centre study approach using non-parametric tests for central tendency. Results:Anti-TNF medication produced a significantly impaired humoral immune response to vaccination against COVID-19. The maximum immune response was detected in 77.4% of control patients, whereas this decreased to 62.2% in participants treated with TNF inhibitors (P = 0.045; effect size, d = 0.194). Patients on combination treatment (anti-TNF medication and MTX, 17 of 45 subjects in the treatment group) did not differ significantly regarding humoral immune response compared with patients on monotherapy with TNF inhibitors only (P = 0.214). Conclusion:TNF inhibitors significantly reduce the humoral response following dual vaccination against COVID-19 in patients with RA.

Zusammenfassung Hintergrund Seit dem 1. März 2017 ist medizinisches Cannabis (MC) bundesweit verschreibungsfähig. Zur Wirksamkeit von MC bei Fibromyalgiesyndrom (FMS) existieren bisher einige qualitativ unterschiedliche Studien. Fragestellung Ziel der Untersuchung war, die Wirksamkeit von Tetrahydrocannabinol (THC) im Verlauf einer IMST hinsichtlich des Schmerzes und mehrerer psychometrischer Variablen zu untersuchen. Material und Methoden Für die Studie wurden im Studienzeitraum (2017–2018) alle Patienten einer Schmerzstation, die an einem FMS erkrankt waren und in einem multimodalen, interdisziplinären Setting behandelt wurden, entsprechend den Einschlusskriterien selektioniert. Die Patienten wurden getrennt nach Gruppen mit und ohne THC-Medikation bzgl. der Schmerzintensität, verschiedener psychometrischer Parameter und des Analgetikaverbrauchs während des Aufenthalts untersucht. Ergebnisse Von den 120 in die Studie eingeschlossenen FMS-Patienten wurden 62 Patienten (51,7 %) mit THC behandelt. In den Parametern Schmerzintensität, Depressivität und Lebensqualität zeigte sich eine signifikante Besserung der Gesamtgruppe während des Aufenthalts ( p < 0,001), die durch den Einsatz von THC signifikant stärker ausfiel. In fünf der sieben untersuchten Analgetikagruppen konnte bei den mit THC behandelten Patienten signifikant häufiger die Dosis reduziert bzw. das Medikament abgesetzt werden. Schlussfolgerung Die Ergebnisse liefern Hinweise dafür, dass THC als medikamentöse Alternative in Ergänzung zu den bisher in verschiedenen Leitlinien empfohlenen Substanzen für die Therapie des FMS in Betracht gezogen werden kann.

Improvement of health‐related quality of life (HRQoL) is frequently reported as a benefit when treating hepatitis C virus infection (HCV) with direct acting antivirals (DAA). As most of the available data were obtained from clinical trials, limited generalizability to the real‐world population might exist. This study aimed to investigate the impact of DAA therapy on changes in HRQoL in a real‐world setting. HRQoL of 1180 participants of the German Hepatitis C‐Registry was assessed by Short‐Form 36 (SF‐36) questionnaires. Scores at post‐treatment weeks 12–24 (FU12/24) were compared to baseline (BL). Changes of ≥2.5 in mental and physical component summary scores (MCS and PCS) were defined as a minimal clinical important difference (MCID). Potential predictors of HRQoL changes were analysed. Overall, a statistically significant increase in HRQoL after DAA therapy was observed, that was robust among various subgroups. However, roughly half of all patients failed to achieve a clinically important improvement in MCS and PCS. Low MCS ( p < .001, OR = 0.925) and PCS ( p < .001, OR = 0.899) BL levels were identified as predictors for achieving a clinically important improvement. In contrast, presence of fatigue ( p = .023, OR = 1.518), increased GPT levels ( p = .005, OR = 0.626) and RBV containing therapy regimens ( p = .001, OR = 1.692) were associated with a clinically important decline in HRQoL after DAA therapy. In conclusion, DAA treatment is associated with an overall increase of HRQoL in HCV‐infected patients. Nevertheless, roughly half of the patients fail to achieve a clinically important improvement. Especially patients with a low HRQoL seem to benefit most from the modern therapeutic options.

Only limited data are available, regarding the influence of IFN-free, DAA-mediated therapy on patient reported outcomes (PROs) and clinical symptoms in patients with chronic hepatitis C infection. Therefore, we longitudinally assessed Short-Form 36 (SF-36) scores in HCV patients antivirally treated in a real world setting and focused on the identification of subgroups especially profiting from DAA regimens with respect to self-reported quality of life (QoL).

The prognostic significance of early diagnosis and therapeutic intervention in inflammatory rheumatic diseases has been well documented. However, a shortage of rheumatologists often impedes this approach in clinical practice. Therefore, it is of importance to identify those patients referred for diagnosis who would benefit most from a specialist's care. We applied a telephone-based triage for appointment allocation during routine care. This retrospective, monocentric analysis evaluated the efficacy of our triage to identify patients with rheumatic disease with special regard to initial appointment category (elective, early arthritis clinic (EAC), or emergency appointment). Of the 1,782 patients assessed, 718 (40.3%) presented with an inflammatory rheumatic disease, and there were significant discrepancies between the appointment categories: elective 26.2%, EAC 49.2% ( P < 0.001) and emergency appointment 56.6% ( P < 0.001). We found that 61.2% of patients were allocated to the correct diagnostic category (inflammatory or noninflammatory) solely based on the telephone-based triage and 67.1% based on the combination of triage and C-reactive protein (CRP) count.

Earlier studies have suggested neurocognitive impairment in patients with chronic hepatitis C virus (HCV) infection even before liver cirrhosis has developed. Since these deficits might be reversible after successful antiviral therapy, we analyzed the long-term course of neurocognitive parameters in HCV patients with and without successful virus elimination by an interferon-based antiviral treatment. In a multicenter study including 168 HCV patients receiving antiviral therapy (peginterferon alpha-2b and ribavirin) we performed a long-term follow-up of neurocognitive performance before and after treatment. Neurocognitive function was psychometrically assessed using the computer-aided TAP (Test Battery of Attentional Performance). When tested at least 12 months after termination of antiviral treatment, patients with sustained virologic response (SVR) had improved significantly as compared to their pretreatment performance in three of five TAP subtasks (vigilance, P < 0.001; shared attention: optical task, P < 0.001; working memory, P < 0.001). Patients who failed to eradicate the virus, however, showed no significant long-term changes in neurocognitive performance in all five subtasks assessed (0.194 < P < 0.804). In the posttreatment evaluation, neurocognitive function was significantly better in responders to the antiviral therapy as compared to nonresponders. Conclusion : Successful eradication of HCV leads to a significant improvement of relevant aspects of attentional and neurocognitive performance, indicating that the neurocognitive impairment caused by chronic HCV infection is potentially reversible. This therefore suggests an added therapeutic benefit of antiviral treatment in HCV infection. Improvement of neurocognitive function may be an additional treatment indication in patients with HCV. (HEPATOLOGY 2013;58:497–504)

Desalination plants are processing huge quantities of sea water for the production of high quality potable and process water. With regard to environmental impact the main concerns are the increased temperature and salinity of the process effluent (brine, cooling water) which has to be rejected to the sea.Many national and international environmental regulations and guidelines are Stipulating discharge limits for temperature and salinity to be complied with by the projected desalination plant in order to obtain the environmental approval for operation. The World Batik guidelines, as well as many national regulations, assume a so called "Mixing Zone" around the point of water discharge, within which initial mixing with ambient sea water takes place, and Stipulate limits for temperature and salinity increase over ambient conditions at the edge of this mixing zone.However, the size of this mixing zone is not clearly defined and the procedures by which the temperature and salinity values are to be determined are missing. In consequence compliance with the stipulated discharge limits can hardly be proven in quantitative terms and the results of Environmental Impact Assessment (EIA) reports are usually rather imprecise in this regard.This presentation describes in a simplified manner an alternative approach for assessment of the environmental impact and corresponding limitation of temperature and salinity increase due to water discharge from desalination and power plants, which is considered more adequate for this purpose. It is proposed to Substitute the Unclear criterion of a "Mixing Zone" size by the water Volume available for dilution of the discharged effluent. A basic procedure for the determination of a minimum dilution water Volume is outlined, considering the temperature or salinity increase between intake and outfall and the discharged water flow rate.The described general approach may be considered by both environmental authorities stipulating discharge limits and the responsible project parties to enable a more adequate assessment regarding compliance of a desalination project with applicable environmental regulations on a sound data basis.

Background and Aim:Approximately 20-30% of chronically infected HCV patients have persistently normal alanine transaminase (PNALT) levels.Histological disease in HCV patients in relation to newly defined upper limits of normal (ULN; 19 IU/ml for females and 30 IU/ml for males) has not been previously studied and we aimed to assess the histological changes in these patients in relation to those with varying degrees of persistently elevated ALT (PEALT).Patients and Methods: Total of 910 HCV patients with available histology from five centres in Saudi Arabia and Canada were categorised into four groups: Group 1 (N = 122) PNALT within the updated ULN (0.5×ULN [corresponding to ≤19 IU/L] for females; 0.75×ULN [corresponding to ≤30 IU/L] for males); Group 2 (N = 170): patients with PNALT ≤1×ULN but >Group 1; Group 3 (N = 311): consecutive, unselected HCV patients with PEALT 1-2×ULN; Group 4 (N = 307): PEALT >2×ULN.PNALT and PEALT were defined as those with three or more determinations identified to be within their respective range over six months or longer.Liver Histology was based on the METAVIR system.Results: Males were more likely to be in Group 1 (73%) while females were more likely to be in Group 2 (58%).Overall, 18 patients (2%) had normal histology, equally divided between PNALT and PEALT.Prevalence of advanced fibrosis (F3-4) was more frequent in patients with PEALT (42%) compared to PNALT (25%).Presence of ≥A2 necroinflammation across groups 1-4 was 48%, 52%, 68% and 76%, respectively.Similarly, ≥F2 fibrosis was seen in 45%, 55%, 64% and 77% of patients across groups 1-4, respectively.Stepwise regression analysis identified age (P = 0.006), gender (P = 0.04), presence within Group 4 (P = 0.004), AST (P = 0.03), platelets (P = 0.003) and genotype (P = 0.003) as independent predictors of histological grade ≥A2, while age (P = 0.0001), AST (P = 0.01), platelets (P = 0.003) and steatosis (P = 0.04) as predictors of significant fibrosis.Conclusions: HCV patients with ALT within the newly-defined "normal" range have the lowest prevalence of histologically significant disease although, utilizing these levels without resorting to liver biopsy may miss significant disease in half the patients.Further analysis will be performed and presented.

Background & Aims: Interferon-associated depression is a frequent side effect of antiviral therapy for chronic hepatitis C. The aim of the present study was to investigate the correlation between platelet serotonin (5-hydroxytryptamine, 5-HT) concentrations and IFN-induced depression.Methods: The study represents a secondary analysis of a previously published trial on the efficacy of SSRI medication in HCV patients on IFN therapy. Ninety-three patients were longitudinally assessed for depression and platelet serotonin. Evaluation time points were: prior to IFN therapy, at weeks 4, 12, and 24 of IFN treatment, and 4 weeks after antiviral treatment. Depression was assessed using the Hospital Anxiety and Depression Scale (HADS). Platelet serotonin concentrations were measured by ELISA.Results: Platelet serotonin concentrations were significantly decreased during interferon therapy (p = 0.001) in 74 of the 93 patients (79.6%). Clinically relevant depression occurred in 33.3% of patients - however, IFN-induced depression was not Significantly linked to either baseline 5-HT concentrations or kinetics. In the subgroup of patients with IFN-induced depression who received the selective serotonin reuptake inhibitor (SSRI) citalopram (20 mg daily, n = 17), serotonin levels declined further during anti-depressant medication, becoming statistically significant within the first 2 weeks (p < 0.001) of SSRI treatment.Conclusions: We demonstrate a significant impact of IFN and SSRI intake on platelet serotonin levels, suggesting a biochemical analogy between 5-HT metabolism in blood platelets and the CNS. Platelet 5-HT levels might serve as a surrogate marker for patient adherence to antiviral and anti-depressant medication. For the prediction of IFN-induced depression, however, platelet 5-HT measurements are not suitable. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.