Analyse internationaler Leitlinien hinsichtlich der Rolle systemischer Glukokortikoide in der medikamentösen Behandlung der rheumatoiden Arthritis

Ziel. Ziel dieser Arbeit ist es, die aktuelle Rolle systemischer Glukokortikoide (GC) in der Behandlung der rheumatoiden Arthritis (RA) zu evaluieren, die Qualität aktueller RA Leitlinien im Allgemeinen sowie der glukokortikoidspezifischen Empfehlungen im Speziellen zu bewerten und hieraus offene Fragen für zukünftige Leitlinien und Forschungsprojekte abzuleiten. Methoden. Es wurde eine systematische Suche nach Leitlinien zur medikamentösen Behandlung der rheumatoiden Arthritis in den medizinischen Datenbanken PubMed Medline, Ovid EMBASE und Cochrane Library durchgeführt, ergänzt durch eine umfassende Handsuche nach grauer Literatur. Alle so erhaltenen Artikel wurden einer gründlichen Qualitätsbewertung mittels des Appraisal of Guidelines for Research and Evaluation (AGREE) II Tools unterzogen, einem state-of-the-art Werkzeug zur Qualitätsbewertung klinischer Leitlinien. Artikel von unzureichender Qualität wurden von der weiteren Analyse ausgeschlossen. Die eingeschlossenen Artikel wurden auf alle relevanten Informationen bezüglich der Anwendung von Glukokortikoiden untersucht, einschließlich der jeweils angeführten Indikationen für eine Glukokortikoidtherapie, der Behandlungsparameter sowie der Punkte, für die ein Mangel an ausreichender Evidenz beschrieben wird. Ergebnisse. Alle eingeschlossenen Leitlinien bewerten Glukokortikoide als angemessene Option für die Behandlung der rheumatoiden Arthritis, insbesondere bei geringer Dosis und kurzer Behandlungsdauer. Viele Empfehlungen versäumen es jedoch, klare und eindeutige Empfehlungen für die Anwendung von Glukokortikoiden bei der RA zu geben: eine exakte Dosis oder Behandlungsdauer wird häufig nicht spezifiziert und die existierende Nomenklatur nicht einheitlich verwendet. Zahlreiche wichtige Aspekte der Glukokortikoidtherapie wie patientenspezifische Faktoren (z.B. Alter, Geschlecht, Begleiterkrankungen), Zeitpunkt der Glukokortikoidgabe (morgens oder abends) oder die genau zu verwendende Substanz (z.B. konventionelles Prednisolon oder solches mit verzögerter Freisetzung) werden kaum adressiert oder überhaupt nicht berücksichtigt. Die Hälfte der Leitlinien beklagt einen Mangel an verlässlicher und detaillierter Evidenz, hauptsächlich bezüglich der langfristigen Sicherheit bzw. des langfristigen Nutzens, der optimalen Ausschleichstrategie sowie der optimalen Therapiedauer. Die Qualitätsbewertung mittels AGREE II offenbarte Mängel in zahlreichen Artikeln, sowohl hinsichtlich der glukortikoidspezifischen Empfehlungen, als auch hinsichtlich der generellen Qualität der Leitlinien. Fazit. Sowohl RA Leitlinien im Allgemeinen als auch die glukokortikoidspezifischen Empfehlungen im Speziellen weisen aktuell entscheidenden Verbesserungsbedarf auf. Hierzu bedarf es der Berücksichtigung zahlreicher bisher nahezu vollkommen vernachlässigter Aspekte, einer einheitlichen Verwendung der existierenden Nomenklatur sowie klarer Empfehlungen zu Dauer, Dosierung und Ausschleichen der Glukokortikoidtherapie. Um dies zu ermöglichen sind weitere Studien zu den zahlreichen noch nicht abschließend geklärten Fragen dringend notwendig.Objective. The aim of this review is to assess the current role of systemic glucocorticoids (GCs) in the management of rheumatoid arthritis (RA), to evaluate the quality of current RA guidelines as well as the appropriateness of GC specific recommendations and to identify open questions that need to be covered by future guidelines and research projects. Methods. We conducted a systematic literature search in the medical databases PubMed Medline, Ovid EMBASE and Cochrane Library for guidelines and consensus statements on the pharmacological treatment of RA, complemented by an extensive hand search for grey literature. All retrieved articles were subjected to a thorough quality appraisal using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool, a state-of-the-art tool for the evaluation of clinical guidelines, and those of insufficient quality were excluded from further analysis. Subsequently, the remaining articles were scrutinized for all relevant information concerning the use of GC, including the provided indications for GC therapy, treatment parameters and points mentioned to be still lacking sufficient evidence. Results. There is general consent that glucocorticoids constitute an appropriate option for the management of RA, in particular if given at low dosages and for a short duration. However, many guidelines fail to provide clear and unambiguous recommendations for the use of GCs in RA as exact dosages and treatment durations are predominantly not specified and existing nomenclature is not used uniformly. Several important aspects of GC therapy, like patient-specific factors (e.g. age, sex, comorbidities), timing of GC administration (morning or evening) or the exact substance to be used (e.g. conventional or modified-release prednisone) are hardly addressed or not even considered by any of the examined articles. Half of the guidelines describe a lack of reliable and detailed evidence, mainly concerning long-term benefit and safety, optimal tapering strategy and optimal duration of GC therapy. The quality appraisal using AGREE II revealed flaws in many articles, concerning GC-specific recommendations as well as guideline quality in general. Conclusion. Recommendations for the use of GCs in RA are in need of decisive improvements. Several aspects which have been neglected to date must be considered, existing nomenclature should be used uniformly and clear recommendations regarding duration, dosage and tapering of GC therapy are necessary. To facilitate this, further studies concerning numerous still unanswered questions are urgently required

Applicability of trials in rheumatoid arthritis and osteoarthritis: A systematic review and meta-analysis of trial populations showing adequate proportion of women, but underrepresentation of elderly people

Objectives: To evaluate whether elderly people and women are adequately represented in randomized controlled trials (RCT) in rheumatoid arthritis (RA) and osteoarthritis (OA). Methods: Four systematic searches in MEDLINE yielded RCT in RA and OA on any intervention published in 2016 and 2017 and population-based studies (PBS) in RA and OA published between 2013 and 2017. Random effects meta-analyses estimated the pooled proportion of elderly people (defined as being ≥ 65 years old), the mean age, its standard deviation (SD), and the proportion of women stratified by disease (RA and OA) and study type (RCT and PBS). Stratified estimates were subsequently compared. Results: 265 RCT comprising 51,240 participants and 53 PBS comprising 523,630 participants were included. In both RA and OA, RCT included lower proportions of elderly people than PBS: RA –0.18 (95% confidence interval –0.22 to –0.13); OA –0.20 (–0.30 to –0.09); had lower mean ages: RA –5.2 years (–6.8 to –3.5); OA –4.7 years (–7.5 to –2.0); and smaller SD: RA –1.9 years (–2.6 to –1.3); OA –2.7 years (–4.2 to –1.2); (all comparisons: p ≤ 0.001). Proportions of women were comparable in RCT compared to PBS in both RA and OA. Conclusions: While women are adequately represented in RA and OA trials, the elderly are underrepresented, probably limiting applicability of current evidence to this growing subgroup. It is urgent to improve the inclusion of elderly people in clinical trials and study age as a determinant for outcome

Recruitment and Retention of Older People in Clinical Research: A Systematic Literature Review

OBJECTIVE: To identify barriers and solutions for the recruitment and retention of older (aged ≥65 years) people in clinical trials. DESIGN: Systematic literature review. METHODS: Three databases (Medline, Embase, and CENTRAL) were searched for articles reporting on barriers or solutions regarding the recruitment or retention of older people. Only original research articles were included. RESULTS: Fifty eligible articles were identified. Exclusion criteria were the most common cause of poor recruitment of older adults (mainly age and comorbidities). Patients' families or physicians often advised against participation (22% of included studies). Lack of interest (18%) and problems with transportation (18%) were also commonly cited as challenges. Fourteen trials (28%) reported that monitoring and adapting their recruitment methods helped, along with a flexible research team (26%) and provision of transportation (24%). Retention was impaired by death (12%), illness (8%), and loss of interest (6%). Methods with a positive effect on retention included financial incentives and regular information about the progress of the study (12%), a low staff turnover (12%), flexibility in appointment making (10%), and expression of appreciation by the staff through letters, gifts, and cards to the participants (10%). CONCLUSION: We identified several barriers and have listed potential solutions that may improve recruitment and lead to fewer dropouts in trials involving older populations. Implementation of our findings may help mitigate the manifold challenges that come with running a trial with older people

Analysis of hip joint loading during walking with different shoe types using instrumented total hip prostheses

Hip joint loads need careful consideration during postoperative physiotherapy after joint replacement. One factor influencing joint loads is the choice of footwear, but it remains unclear which footwear is favorable. The objective of the present study was to investigate the influence of footwear on hip joint loads in vivo. Instrumented hip endoprostheses were used for in vivo load measurements. The parameters resultant contact force (F-res), bending moment (M-bend) and torsional moment (M-tors) were evaluated during treadmill walking at 4 km/h with different shoe types. In general, footwear tended to increase hip joint loading, with the barefoot shoe having the least influence. F-res and M-bend were significantly increased during heel strike for all shoe types in comparison to barefoot walking, with everyday shoe (34.6%; p=0.028 and 47%; p=0.028, respectively) and men's shoe (33.2%; p=0.043 and 41.1%; p=0.043, respectively) resulting in the highest changes. M-tors at AbsMax was increased by all shoes except for the barefoot shoe, with the highest changes for men's shoe (+17.6%, p=0.043) and the shoe with stiffened sole (+17.5%, p=0.08). Shoes, especially those with stiff soles or elaborate cuishing and guiding elements, increase hip joint loads during walking. The influence on peak loads is higher for M-tors than for F-res and M-bend. For patients in which a reduction of hip joints loads is desired, e.g. during physiotherapy after recent surgery or to alleviate symptoms of osteoarthritis, low profile shoes with a flexible sole may be preferred over shoes with a stiff sole or elaborate cushioning elements

Association Between Participant Retention and the Proportion of Included Elderly People in Rheumatology Trials: Results From a Series of Exploratory Meta‐Regression Analyses

Objective. The elderly, a population defined by an age of ≥65 years, are underrepresented in rheumatology trials, possibly due to investigators' concerns of increased premature discontinuations in higher age groups. The present study was undertaken to evaluate whether the proportion of included elderly individuals (PE) is independently associated with participant retention in rheumatology trials. Methods. Medline was searched for randomized controlled trials (RCTs) in rheumatoid arthritis (RA) and osteoarthritis (OA) of any intervention (years 2016 and 2017). PE was either extracted from the research manuscript or estimated from an assumed (truncated) normal distribution. We used mixed-effects meta-regression models including several covariates to assess whether there is an independent association between PE and participant retention. Using sensitivity analyses, we evaluated whether associations were connected to attrition due to lack of efficacy (LoE) or adverse events (AE). Results. In total, 243 RCTs comprising >48,000 participants were included. Pooled participant retention was 88%. PE was not associated with retention in the unadjusted (P = 0.97) or adjusted (all: P ≥0.14) models. Of all covariates, only study duration and type of intervention were associated with retention (both: P < 0.001). Post hoc analyses allowing for interaction revealed a small but statistically significant positive association between PE and retention in pharmacologic interventions and a negative association in physical/physiotherapeutic interventions (overall P for interaction = 0.05). No associations were found for PE and attrition due to LoE or AE. Conclusion. Participant retention in RA and OA trials is high and not associated with PE. These findings should motivate investigators to include more elderly participants in rheumatology trials

In vivo analysis of hip joint loading on Nordic walking novices

Objective: To evaluate the influence of Nordic walking (NW) on hip joint loads in order to determine whether it can be safely performed during postoperative physiotherapy in patients after orthopeadic surgery of the hip. Methods: Internal hip joint loads were directly measured in vivo in 6 patients using instrumented hip prostheses during NW and ordinary walking (OW). All patients received training in two different NW techniques (double-poling and the diagonal technique) by a certified NW instructor. Measurements were conducted on a treadmill at a speed of 4 km/h on level ground, at 10% inclination and at 10% slope as well as on a level lawn at a self chosen comfortable speed. Resultant contact force (F-res), bending moment (M-bend) and torsional torque (M-tors) were compared between NW and OW as well as between both NW techniques. Results: Joint loads showed a double peak pattern during all setups. Neither NW technique significantly influenced hip joint loads at the time of the first load peak during contralateral toe-off (CTO), which was also the absolute load peak, in comparison to OW. Compared to OW, double-poling significantly reduced F-res and M-bend at the time of the second load peak during the contralateral heel strike (CHS) on level ground both on the treadmill (- 6% and - 7%, respectively) and on the lawn (- 7% and - 9%). At 10% inclination, the diagonal technique increased F-res and M-bend at CHS (by + 6% and + 7%), but did not increase the absolute load peak at CTO. Conclusion: Joint loads during NW are comparable to those of OW. Therefore, NW can be considered a low-impact activity and seems to be safe for patients that are allowed full weight bearing, e.g. during postoperative rehabilitation after THA

Kyphoplasty Restores the Global Sagittal Balance of the Spine Independently from Pain Reduction

Kyphoplasty is the standard surgical treatment of vertebral compression fractures. We aimed to clarify the influence of kyphoplasty on the sagittal profile as well as the relation between posture improvement and pain relief. For this purpose, we evaluated various radiological parameters of the sagittal profile on whole spine standing radiographs of 73 Patients with a single vertebral fracture treated by kyphoplasty. The key outcome was the postoperative change of the sagittal vertical axis (SVA). Additionally, clinical parameters including pain scores on visual analogue scale (VAS) and use of analgesics were obtained from medical records. Pre- and postoperative radiological as well as clinical parameters were compared. Additionally, the correlation between changes of SVA and changes of local kyphotic angle (LKA) or VAS was examined. The clinical parameters as well as various radiographic parameters (SVA, LKA, Gardner, Cobb) improved significantly postoperatively. The improvement of SVA correlated significantly with the correction of the LKA but not with postoperative pain relief. We conclude that kyphoplasty helps to restore the global sagittal balance of the spine after vertebral fractures. The correction of the sagittal profile seems to depend on the correction of the local kyphotic angle but does not correlate with postoperative pain relief

Musculature adaption in patients with lumbosacral transitional vertebrae: a matched-pair analysis of 46 patients

Objective: Even though lumbosacral transitional vertebrae (LSTV) are one of the most common congenital anomalies of the spine, their effect on surrounding soft tissues is not well-studied. We therefore aimed at analyzing the association between LSTV and changes in volume, mass, symmetry, and degeneration of lumbar and trunk muscles. Materials and methods: Abdomen-pelvis CT scans were analyzed in patients with LSTV and a matched control group. LSTV were classified according to the Castellvi classification. Muscles were segmented from the remaining soft tissue and their cross-sectional area and volume were examined at five defined levels. Threshold segmentation was used to differentiate between muscle fibers and fat tissue. Matched pairs were compared using Wilcoxon rank sum tests. For comparison of categorical data, chi-squared tests were performed and for associations between the degree of fusion and muscle size and degeneration, Spearman's correlation coefficients were calculated. Inter- and intrarater reliabilities were evaluated by computing intraclass correlation coefficients. Results: Forty-six patients with LSTV and 46 controls were included. Muscle volume of the paraspinal and trunk muscles was significantly lower (707.0 cm(3) vs. 809.7 cm(3), p < 0.001) and fatty muscle changes were significantly increased in all but the caudal paravertebral muscles of LSTV patients (M. psoas p < 0.04, M. quadratus lumborum p < 0.001, paravertebral muscles p = 0.011, M. rectus abdominis p < 0.001, M. obliquus abdominis p < 0.001). Correlations between the degree of Castellvi classification and muscle volume were significant (p = 0.001). Conclusion: LSTV are associated with a reduction in muscle volume and an increase in muscle degeneration of both lumbar and trunk muscles

Influence of operative timing on the early post-operative radiological and clinical outcome after kyphoplasty

Purpose: To clarify the relationship between operative timing and the early post-operative radiological and clinical outcome after kyphoplasty. Methods: We conducted a retrospective cohort study including patients who underwent kyphoplasty of a single vertebra. Patients were divided into three groups (acute [< 2 weeks], subacute [2–6 weeks] or chronic [6–51 weeks]) based on the interval between fracture and surgery. The relative vertebral body height (VBH) and local kyphotic angle (LKA) of the fractured vertebra (measured on plain radiographs) as well as pain and use of analgesics were compared pre- and post-operatively (day 2) and between the groups. Results: A total of 230 patients (100 with acute, 91 with subacute and 39 with chronic fractures) with fractures from T4 to L5 were included. In all groups, there was a significant post-operative improvement in the anterior (8.9–12.9%) and middle (10.7–13.4%) VBH (all groups: p < 0.001), LKA (acute: 3.8°, p < 0.001; subacute: 4.3°, p < 0.001; chronic: 1.7°, p = 0.046) and pain. The use of analgesics significantly decreased post-operatively in the acute and subacute groups, but did not significantly change in the chronic group. Patients from acute (p = 0.042) and subacute (p = 0.027) groups showed significantly better post-operative correction of the LKA than the chronic group. Conclusion: Kyphoplasty is effective for vertebral height restoration as well as pain relief for both acute, subacute and chronic fractures. However, the achievable correction of the fracture-related local kyphosis decreases significantly after 6 weeks. Therefore, we recommend making a final decision about conservative vs. operative treatment within 6 weeks to ensure better height restoration in surgically treated patients

Vertebral disk morphology of the lumbar spine: a retrospective analysis of collagen-sensitive mapping using dual-energy computed tomography

Objectives: To investigate the diagnostic accuracy of collagen-sensitive maps derived from dual-energy computed tomography (DECT) for the detection of lumbar disk pathologies in a feasibility setting. Materials and methods: We retrospectively reviewed magnetic resonance imaging (MRI), computed tomography (CT), and DECT datasets acquired in patients who underwent periradicular therapy of the lumbar spine from June to December 2019. Three readers scored DECT collagen maps, conventional CT, and MRI for presence, type, and extent of disk pathology. Contingency table analyses were performed to determine diagnostic accuracy using MRI as standard of reference. Interrater agreement within and between imaging modalities was evaluated by computing intraclass correlation coefficients (ICCs) and Cohen’s kappa. Correlation between sum scores of anteroposterior disk displacement was determined by calculation of a paired t test. Results: In 21 disks in 13 patients, DECT had a sensitivity of 0.87 (0.60–0.98) and specificity of 1.00 (0.54–1.00) for the detection of disk pathology. Intermodality agreement for anteroposterior disk displacement was excellent for DECT (ICC 0.963 [0.909–0.985]) and superior to CT (ICC 0.876 [0.691–0.95]). For anteroposterior disk displacement, DECT also showed greater within-modality interrater agreement (ICC 0.820 [0.666–0.916]) compared with CT (ICC 0.624 [0.39–0.808]). Conclusion: Our data suggest that collagen-sensitive imaging has an added benefit, allowing more accurate evaluation of the extent of disk displacement with higher interrater reliability. Thus, DECT could provide useful diagnostic information in patients undergoing CT for other indications or with contraindications to MRI