Wirksamkeit, Zweckmäßigkeit und Wirtschaftlichkeit des multimodalen Behandlungsansatzes bei chronisch lumbalen Rückenschmerzen

Zusammenfassung: Hintergrund: Der Nachweis der Behandlungskriterien Wirksamkeit, Zweckmäßigkeit und Wirtschaftlichkeit ist bei chronisch lumbalen Rückenschmerzen ["chronic low back pain" (CLBP)] notwendig, da Kostenträger die Übernahme von Behandlungskosten hiervon abhängig machen. Material und Methoden: Eine systematische Literatursuche zu den Behandlungskriterien der interdisziplinären, multimodalen Schmerztherapie ["multidisciplinary treatment" (MDT)] bietet einen Überblick über die aktuelle Literatur zur Behandlung von CLBP. Ergebnisse: Auf die moderate Wirksamkeit von MDT weisen 8Übersichtsarbeiten hin, wenn auch mit einigen Einschränkungen. Die Ergebnisse von 6 bisher in keine Übersichtsarbeit eingeschlossenen Originalarbeiten stützen die Ergebnisse der Übersichtsarbeiten. Die Langzeitergebnisse von MDT und operativen Behandlungen sind, bei höheren Kosten und Risiken für operative Behandlungen, vergleichbar. Die Wirtschaftlichkeit von MDT erreicht in 3Originalarbeiten eine moderate bis hohe Evidenz. Schlussfolgerungen: MDT sind sowohl moderat wirksam als auch wirtschaftlich. Daher sind sie eine kostengünstigere Behandlungsalternative zu operativen Verfahre

Baseline musculoskeletal pain and impaired sleep related to school pressure influence the development of musculoskeletal pain in N = 107 adolescents in a 5-year longitudinal study

Purpose: This longitudinal study followed 10- to 13-year-old adolescents for five years to investigate the effects of juvenile musculoskeletal (MSK) pain and psychosocial risk factors on future pain. We further predicted that increased MSK pain at follow-up would be positively related to current school pressure at follow-up and negatively related to current sleep quality. Sleep quality was tested as a potential mediator of the link between school pressure and MSK pain at follow-up after controlling for baseline MSK pain. Methods: The baseline sample comprised 189 adolescents and five-year follow-up resulted in 107 15- to 18-year-old adolescents who had completed mandatory education. Adolescents responded to an online questionnaire about psychosocial stressors, MSK pain, school achievement, and leisure activities. A longitudinal hierarchic linear regression including all significant baseline predictors was run to assess their impact on MSK pain five years later. Mediation analysis was used to investigate sleep quality as a potential mediator of the relationship between school pressure and MSK pain at follow-up. Results: Baseline MSK pain predicted MSK pain over a time lag of five years (ß = .26, p = .02). The relationship between follow-up school pressure and current MSK pain was mediated by sleep quality at follow-up (B = .17, SEB = .07, CI-95 = .06 to .34) when baseline MSK pain was controlled. Conclusions: Juvenile MSK pain predicts MSK pain in adolescence. A psychosocial mediation model including school pressure and sleep impairments has the potential to explain MSK pain mechanisms in adolescents

Identification of prognostic factors for chronicity in patients with low back pain: a review of screening instruments

Low back pain (LBP) is currently the most prevalent and costly musculoskeletal problem in modern societies. Screening instruments for the identification of prognostic factors in LBP may help to identify patients with an unfavourable outcome. In this systematic review screening instruments published between 1970 and 2007 were identified by a literature search. Nine different instruments were analysed and their different items grouped into ten structures. Finally, the predictive effectiveness of these structures was examined for the dependent variables including "work status", "functional limitation”, and "pain". The strongest predictors for "work status” were psychosocial and occupational structures, whereas for "functional limitation” and "pain” psychological structures were dominating. Psychological and occupational factors show a high reliability for the prognosis of patients with LBP. Screening instruments for the identification of prognostic factors in patients with LBP should include these factors as a minimum core se

Resources for preventing sickness absence due to low back pain

Background After an episode of non-specific low back pain (LBP) some individuals fail to return to work. The factors leading to such LBP-related sickness absence are not yet fully understood. Aims To identify individual resources, over and above the already established predictors, for preventing LBP-related sickness absence in a population-based sample of workers experiencing an episode of LBP. Methods Cohort study with 1-year follow-up. Participants were from a working population who reported an episode of acute or subacute LBP at baseline. Four potential resources—life satisfaction, doing sports, job satisfaction and social support at work—were examined for their incremental value in predicting sickness absence over and above baseline sickness absence and fear-avoidance beliefs about work. Results In all, 279 workers participated in the study. All four resources showed an inverse relationship with regard to sickness absence. A multiple regression analysis revealed that life satisfaction as a resource protected against sickness absence, when controlling for established risk factors. Job satisfaction and social support at work minimized the influence of sickness absence at baseline and at 1-year follow-up. Conclusions In a non-clinical working sample of individuals experiencing an acute/subacute episode of LBP, life satisfaction was a unique predictor of sickness absence after 1 year. Prevention in the occupational setting should not only address common risk factors but also occupational and individual resources that keep workers satisfied with life despite having LB

AMPK alpha 1-induced RhoA phosphorylation mediates vasoprotective effect of estradiol

OBJECTIVE: Estradiol (E2) mediates numerous beneficial effects assigned to estrogens, but whereas mechanisms have been described at the endothelial level, direct effects on vascular smooth muscle cells (VSMC) are poorly documented. As evidence accumulates regarding the role of RhoA in vascular pathophysiology and the benefit of RhoA-Rho associated protein kinase (Rock) pathway inhibition, we analyzed if E2 could inhibit it in VSMC. METHODS AND RESULTS: We show that in VSMC, E2 inhibits the RhoA-Rock pathway in a time- and concentration-dependent manner. The inhibition of RhoA-Rock pathway results from E2-induced phosphorylation of the Ser188 of RhoA. Using pharmacological, transfection, and in vitro phosphorylation experiments, we demonstrate that AMP-activated protein kinase subunit alpha 1 (AMPKalpha1) is activated by estrogen receptor stimulation and catalyzes RhoA phosphorylation induced by E2. Ex vivo, ovariectomy leads to an increase in the amplitude of phenylephrine- or serotonine-induced contractions of aortic rings in wild-type mice but not in AMPKalpha1-knock-out mice or E2-supplemented animals. These functional effects were correlated with a reduced level of RhoA phosphorylation in the aorta of ovariectomized female, male, and AMPKalpha1 knock-out mice. CONCLUSION: Our work thus defines AMPKalpha1 as (1) a new kinase for RhoA and (2) a new mediator of the vasoprotective effects of estrogen

Trimester-specific reference intervals for thyroid function parameters in pregnant Caucasian women using Roche platforms: a prospective study

Background: Standard thyroid function parameters reference intervals (RI) are unsuitable during pregnancy, potentially resulting in incongruous treatments that may cause adverse effects on pregnancy outcomes. We aimed at defining trimester-specific TSH, FT4 and FT3 RI, using samples longitudinally collected from healthy Caucasian women. Materials and methods: Blood samples from 150 healthy Caucasian women, who had a physiological gestation and a healthy newborn at term, were collected in each trimester and at around six months post-partum. They showed mild iodine deficiency. After excluding women with overt TSH abnormalities (> 10 mU/L) and/or TPO antibodies, data from 139 pregnant women were analyzed by means of widely used Roche platforms, and TSH, FT4 and FT3 trimester-specific RI were calculated. Post-partum data were available for 55 subjects. Results: Serum TSH RI were 0.34-3.81 mU/L in the first trimester, and changed slightly to 0.68-4.07 U/L and 0.63-4.00 mU/L in the second and third trimester, respectively. Conversely, both FT4 and FT3 concentrations progressively decreased during pregnancy, the median values in the third trimester being 14.8% and 13.2% lower, respectively, than in the first trimester. Thyroid function parameters in the first trimester were similar to those measured after the end of pregnancy. Conclusions: This study calculates trimester-specific RI for thyroid function parameters in pregnancy, and proposes the reference limits that should be adopted when using Roche platforms in Caucasian women

Proceedings of the Workshop on Monte Carlo's, Physics and Simulations at the LHC PART II

These proceedings collect the presentations given at the first three meetings of the INFN "Workshop on Monte Carlo's, Physics and Simulations at the LHC", held at the Frascati National Laboratories in 2006. The first part of these proceedings contains pedagogical introductions to several basic topics of both theoretical and experimental high pT LHC physics. The second part collects more specialised presentations.Comment: 157 pages, 136 figures; contribution by M. Grazzini has been adde

Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16.

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated

Integrative molecular analysis of combined small-cell lung carcinomas identifies major subtypes with different therapeutic opportunities

Background: Combined small-cell lung cancer (C-SCLC) is composed of SCLC admixed with a non-small-cell cancer component. They currently receive the same treatment as SCLC. The recent evidence that SCLC may belong to either of two lineages, neuroendocrine (NE) or non-NE, with different vulnerability to specific cell death pathways such as ferroptosis, opens new therapeutic opportunities also for C-SCLC. Materials and methods: Thirteen C-SCLCs, including five with adenocarcinoma (CoADC), five with large-cell neuroendocrine carcinoma (CoLCNEC) and three with squamous cell carcinoma (CoSQC) components, were assessed for alterations in 409 genes and transcriptomic profiling of 20 815 genes. Results: All 13 cases harbored TP53 (12 cases) and/or RB1 (7 cases) inactivation, which was accompanied by mutated KRAS in 4 and PTEN in 3 cases. Potentially targetable alterations included two KRAS G12C, two PIK3CA and one EGFR mutations. Comparison of C-SCLC transcriptomes with those of 57 pure histology lung cancers (17 ADCs, 20 SQCs, 11 LCNECs, 9 SCLCs) showed that CoLCNEC and CoADC constituted a standalone group of NE tumors, while CoSQC transcriptional setup was overlapping that of pure SQC. Using transcriptional signatures of NE versus non-NE SCLC as classifier, CoLCNEC was clearly NE while CoSQC was strongly non-NE and CoADC exhibited a heterogeneous phenotype. Similarly, using ferroptosis sensitivity/resistance markers, CoSQC was classified as sensitive (as expected for non-NE), CoLCNEC as resistant (as expected for NE) and CoADC showed a heterogeneous pattern. Conclusions: These data support routine molecular profiling of C-SCLC to search for targetable driver alterations and to precisely classify them according to therapeutically relevant subgroups (e.g. NE versus non-NE)