Polypharmacy among patients with multiple sclerosis: a qualitative systematic review

ABSTRACT

Objectives: The consequences of polypharmacy (intake of ≥ 5 drugs) are diverse, including drug interactions, rising costs and side effects. Risk groups for polypharmacy are multimorbid and chronically ill people, such as patients with multiple sclerosis (MS). MS is the most common neuroimmunological disease in young adults worldwide. We aimed to provide a systematic overview of the current research status regarding frequency and predictors of polypharmacy in MS patients.

Methods: A systematic literature search in the databases PubMed, Cochrane Library and Scopus was carried out according to the PRISMA guidelines. English and German original research articles were included.

Results: Seven studies fulfilled the inclusion criteria of this review, while the research objectives and methods were very heterogenous. The polypharmacy rates in these studies ranged from 15% to 59%. Polypharmacy correlated with comorbidities, increased disability, cognitive deficits, increased hospitalization, higher relapse rate and lower quality of life.

Conclusions: In MS patients, polypharmacy is common and closely associated with health issues. There is a great need for research in this area, especially regarding longitudinal changes in drug utilization. Effective networks between physicians and pharmacists are needed to optimize medication management for patients and to achieve the best possible therapy results.     

Tibial lengthening using a retrograde magnetically driven intramedullary lengthening device in 10 patients with preexisting ankle and hindfoot fusion

Background and purpose — Motorized intramedullary lengthening nails (ILNs) have been developed as an alternative to external fixators for long bone lengthening. The antegrade approach represents the standard method for tibial ILN insertion. In patients with preexisting ankle and hindfoot fusion a retrograde approach provides an alternative technique that has not been evaluated so far. We report the outcome of this method in 10 patients.Patients and methods — This retrospective study included 10 patients (mean age 18 years [13–25]) with preexisting ankle and hindfoot fusion who underwent tibial lengthening with a retrograde ILN (PRECICE). The mean leg length discrepancy (LLD) was 58 mm (36–80). The underlying conditions were congenital (n = 9) and post tumor resection (n = 1). The main outcome measures were: ILN reliability, distraction achieved, distraction index (DIX), time to bone healing, consolidation index (CIX), complications, and functional results.Results — All patients achieved the goal of lengthening (mean 48 mm [26–80]). Average DIX was 0.6 mm/day (0.5–0.7) and mean CIX was 44 days/cm (26–60). Delayed consolidation occurred in 2 patients and healed after ILN dynamization or nail exchange with grafting. Toe contractures in 2 other patients were resolved with physiotherapy or tenotomy. Until last follow-up (mean 18 months [12–30]) no true complications were encountered, knee motion remained unaffected, and full osseous consolidation occurred in all patients.Interpretation — In patients with LLD and preexisting ankle and hindfoot fusion distal tibial lengthening using a retrograde ILN is a reliable alternative to the standard approach with equivalent bone healing potential and low complication rates leaving the knee unaffected.

Fully implantable intramedullary lengthening nails (ILNs) with mechanical (Guichet and Casar 1997, Cole et al. 2001) and motorized (Baumgart et al. 1997, Schiedel et al. 2014) drive systems have been developed as an alternative to external fixators for bone lengthening (Mahboubian et al. 2012, Black et al. 2015, Laubscher et al. 2016). Recently, magnetically driven ILNs in particular have become increasingly popular (Kirane et al. 2014, Wagner et al. 2017) and in contrast to external fixation provide an equally safe and more comfortable option for limb lengthening and deformity correction (Szymczuk et al. 2019, Horn et al. 2019). Antegrade or retrograde femoral and antegrade tibial lengthening with the PRECICE limb lengthening system (NuVasive, San Diego, CA, USA) has been assessed by several studies (Kirane et al. 2014, Schiedel et al. 2014, Shabtai et al. 2014, Tiefenboeck et al. 2016, Wiebking et al. 2016, Fragomen and Rozbruch 2017, Wagner et al. 2017, Iobst et al. 2018, Cosic and Edwards 2020, Nasto et al. 2020).In tibial lengthening the antegrade approach represents the standard method for ILN implantation (Fragomen and Rozbruch 2017). In patients with preexisting ankle and hindfoot fusion a retrograde approach provides an alternative technique for tibial nail insertion. Approach-associated affections of the knee joint like anterior knee pain (Rothberg et al. 2019) and—in immature patients—damage to the proximal tibial growth plate (Wagner et al. 2017, Frommer et al. 2018) can be avoided. Despite these potential advantages, the use of a retrograde tibial nailing approach and distal tibial osteotomy in patients with preexisting ankle and hindfoot fusion has not been evaluated so far.     

Aqua cycling for immunological recovery after intensive,eccentric exercise

Purpose

Alterations in immunological homeostasis induced by acute exercise have been frequently reported. In view of the growing amount of repetitive exercise stimuli in competitive sports, quick recovery plays a superior role. Therefore, we examined whether aqua cycling affects cellular immunological recovery.

Methods

After performing 300 countermovement jumps with maximal effort male sport students (n = 20; 24.4 ± 2.2 years) were randomized into either an aqua cycling (AC) or a passive recovery (P) group. AC pedaled in chest-deep water without resistance, while P lay in a supine position. Each recovery protocols lasted 30 min. Blood samples were taken at Baseline, Post-exercise, Post-recovery and 1 h (h), 2 h, 4 h, 24 h, 48 h and 72 h after recovery. Outcomes comprised white blood cell (WBC) counts, lymphocyte (LYM) counts and LYM subsets (CD4/CD8 ratio). Additionally, cellular inflammation markers (neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and systemic immune-inflammation index (SII)) were calculated.

Results

In both groups, WBC, NLR and SII were significantly increased compared to Baseline up to and including 4 h after recovery. Significant interaction effects were found for WBC (Post-recovery, 2 h and 4 h), NLR (Post-recovery), SII (Post-recovery) and CD4/CD8 ratio (2 h) with values of AC being higher than of P.

Conclusions

Interestingly, AC provoked a stronger but not prolonged immunological disturbance than P. NLR and SII may present simple, more integrative markers to screen exercise-induced alterations in immune homeostasis/recovery in athletes and clinical populations. More research is warranted to elucidate the clinical and practical relevance of these findings.

     

Junger Patient mit ungewöhnlicher Raumforderung am Unterlid

Die Ophthalmologie - Eine Raumforderung der Lider im jungen Erwachsenenalter ist oft ein Zeichen einer Entzündung, eines Traumas oder einer benignen Neoplasie. Ziel dieser Kasuistik ist es,...     

Reproducibility and reliability of central corneal thickness determination in more and less profound corneal edema using ultrasound pachymetry,a Scheimpflug camera and anterior segment OCT

Graefe's Archive for Clinical and Experimental Ophthalmology - The purpose of this study is to determine the influence of different degrees of corneal edema on the reliability and...     

Selective targeting of regulatory T cells with CD28 superagonists allows effective therapy of experimental autoimmune encephalomyelitis

CD4+CD25+ regulatory T cells (T reg cells) play a key role in controlling autoimmunity and inflammation. Therefore, therapeutic agents that are capable of elevating numbers or increasing effector functions of this T cell subset are highly desirable. In a previous report we showed that a superagonistic monoclonal antibody specific for rat CD28 (JJ316) expands and activates T reg cells in vivo and upon short-term in vitro culture. Here we demonstrate that application of very low dosages of the CD28 superagonist into normal Lewis rats is sufficient to induce T reg cell expansion in vivo without the generalized lymphocytosis observed with high dosages of JJ316. Single i.v. administration of a low dose of the CD28 superagonist into Dark Agouti (DA) rats or Lewis rats that suffered from experimental autoimmune encephalomyelitis (EAE) proved to be highly and equally efficacious as high-dose treatment. Finally, we show that T reg cells that were isolated from CD28-treated animals displayed enhanced suppressive activity toward myelin basic protein-specific T cells in vitro, and, upon adoptive transfer, protected recipients from EAE. Our data indicate that this class of CD28-specific monoclonal antibodies targets CD4+CD25+ T reg cells and provides a novel means for the effective treatment of multiple sclerosis and other autoimmune diseases.     

The BCR-ABL1 kinase bypasses selection for the expression of a pre-B cell receptor in pre-B acute lymphoblastic leukemia cells

The BCR-ABL1 kinase expressed in acute lymphoblastic leukemia (ALL) drives malignant transformation of human pre-B cells. Comparing genome-wide gene expression profiles of BCR-ABL1+ pre-B ALL and normal bone marrow pre-B cells by serial analysis of gene expression, many genes involved in pre-B cell receptor signaling are silenced in the leukemia cells. Although normal pre-B cells are selected for the expression of a functional pre-B cell receptor, BCR-ABL1+ ALL cells mostly do not harbor a productively rearranged IGH allele. In these cases, we identified traces of secondary VH gene rearrangements, which may have rendered an initially productive VH region gene nonfunctional. Even BCR-ABL1+ ALL cells harboring a functional VH region gene are unresponsive to pre-B cell receptor engagement and exhibit autonomous oscillatory Ca2+ signaling activity. Conversely, leukemia subclones surviving inhibition of BCR-ABL1 by STI571 restore responsiveness to antigen receptor engagement and differentiate into immature B cells expressing immunoglobulin light chains. BCR-ABL1 kinase activity is linked to defective pre-B cell receptor signaling and the expression of a truncated isoform of the pre-B cell receptor-associated linker molecule SLP65. Also in primary leukemia cells, truncated SLP65 is expressed before but not after treatment of the patients with STI571. We conclude that inhibition of BCR-ABL1 reconstitutes selection for leukemia cells expressing a functional (pre-) B cell receptor.     

Rapid degradation of oseltamivir phosphate in clinical samples by plasma esterases

The anti-influenza drug oseltamivir is an ester prodrug activated by hepatic carboxylesterases. Plasma esterases also convert up to 31.8% of the parent compound to the active metabolite after 4 h ex vivo, with wide interindividual variation. This source of error is removed by adding the esterase inhibitor dichlorvos to blood collection tubes.