Evaluating rehabilitation following lumbar fusion surgery (REFS): study protocol for a randomised controlled trial

BACKGROUND: The rate of lumbar fusion surgery (LFS) is increasing. Clinical recovery often lags technical outcome. Approximately 40% of patients undergoing LFS rate themselves as symptomatically unchanged or worse following surgery. There is little research describing rehabilitation following LFS with no clear consensus as to what constitutes the optimum strategy. It is important to develop appropriate rehabilitation strategies to help patients manage pain and recover lost function following LFS. METHODS/DESIGN: The study design is a randomised controlled feasibility trial exploring the feasibility of providing a complex multi-method rehabilitation intervention 3 months following LFS. The rehabilitation protocol that we have developed involves small participant groups of therapist led structured education utilising principles of cognitive behavioral therapy (CBT), progressive, individualised exercise and peer support. Participants will be randomly allocated to either usual care (UC) or the rehabilitation group (RG). We will recruit 50 subjects, planning to undergo LFS, over 30 months. Following LFS all participants will experience normal care for the first 3 months. Subsequent to a satisfactory 3 month surgical review they will commence their allocated post-operative treatment (RG or UC). Data collection will occur at baseline (pre-operatively), 3, 6 and 12 months post-operatively. Primary outcomes will include an assessment of feasibility factors (including recruitment and compliance). Secondary outcomes will evaluate the acceptability and characteristics of a limited cluster of quantitative measures including the Oswestry Disability Index (ODI) and an aggregated assessment of physical function (walking 50 yards, ascend/descend a flight of stairs). A nested qualitative study will evaluate participants' experiences. DISCUSSION: This study will evaluate the feasibility of providing complex, structured rehabilitation in small groups 3 months following technically successful LFS. We will identify strengths and weakness of the proposed protocol and the usefulness and characteristics of the planned outcome measures. This will help shape the development of rehabilitation strategies and inform future work aimed at evaluating clinical efficacy. TRIAL REGISTRATION: ISRCTN60891364, 10/07/2014

Measurement properties of performance-based instruments to assess mental function during activity and participation in persons who have survived a stroke:a systematic review protocol

BACKGROUND: A frequent consequence of stroke is impaired mental function, which often affects the ability to perform activities and participate in life situation. In occupational therapy practice, performance-based instruments during activity and participation are often used. However, it is important to assess if the instruments used are valid, reliable and responsive.OBJECTIVE: The objective of this systematic review is to investigate measurement properties of performance-based instruments to assess mental function during activity and participation in persons who have survived stroke.MATERIAL AND METHODS: Systematic database searches of PubMed, EMBASE, CINAHL, PsycINFO, and OTseeker will be conducted. COSMIN Risk of Bias checklist will be used to evaluate methodological quality of the included articles. Measurement properties of the included studies will be rated against criteria for good measurement properties. The overall evidence of each measurement property per instrument is graded using a modified GRADE approach.RESULTS: Results will be presented in text and tables.CONCLUSIONS: Conclusion will be drawn up-on the overall evidence to give recommendations on the most suitable instrument.SIGNIFICANCE: It is expected that findings of the review will provide evidence to guide professionals in the selection of a performance-based instruments to measure mental function in practice and research.TRIAL REGISTRATION NUMBER: PROSPERO CRD42018086744.</p

Differential regulation of NF-κB activation and function by topoisomerase II inhibitors

BACKGROUND: While many common chemotherapeutic drugs and other inducers of DNA-damage result in both NF-κB nuclear translocation and DNA-binding, we have previously observed that, depending on the precise stimulus, there is great diversity of the function of NF-κB. In particular, we found that treatment of U-2 OS osteosarcoma cells with the anthracycine daunorubicin or with ultraviolet (UV-C) light resulted in a form of NF-κB that repressed rather than induced NF-κB reporter plasmids and the expression of specific anti-apoptotic genes. Anthracyclines such as daunorubicin can induce DNA-damage though inhibiting topoisomerase II, intercalating with DNA and undergoing redox cycling to produce oxygen free radicals. In this study we have investigated other anthracyclines, doxorubicin and aclarubicin, as well as the anthracenedione mitoxantrone together with the topoisomerase II inhibitor ICRF-193, which all possess differing characteristics, to determine which of these features is specifically required to induce both NF-κB DNA-binding and transcriptional repression in U-2 OS cells. RESULTS: The use of mitoxantrone, which does not undergo redox cycling, and the reducing agent epigallocatechingallate (EGCG) demonstrated that oxygen free radical production is not required for induction of NF-κB DNA-binding and transcriptional repression by these agents and UV-C. In addition, the use of aclarubicin, which does not directly inhibit topoisomerase II and ICRF-193, which inhibits topoisomerase II but does not intercalate into DNA, demonstrated that topoisomerase II inhibition is not sufficient to induce the repressor form of NF-κB. CONCLUSION: Induction of NF-κB DNA-binding and transcriptional repression by topoisomerase II inhibitors was found to correlate with an ability to intercalate into DNA. Although data from our and other laboratories indicates that topoisomerase II inhibition and oxygen free radicals do regulate NF-κB, they are not required for the particular ability of NF-κB to repress rather than activate transcription. Together with our previous data, these results demonstrate that the nature of the NF-κB response is context dependent. In a clinical setting such effects could profoundly influence the response to chemotherapy and suggest that new methods of analyzing NF-κB function could have both diagnostic and prognostic value

Interactions between genes involved in the antioxidant defence system and breast cancer risk

The aim of the study is to examine the association between multilocus genotypes across 10 genes encoding proteins in the antioxidant defence system and breast cancer. The 10 genes are SOD1, SOD2, GPX1, GPX4, GSR, CAT, TXN, TXN2, TXNRD1 and TXNRD2. In all, 2271 cases and 2280 controls were used to examine gene–gene interactions between 52 single nucleotide polymorphisms (SNPs) that are hypothesised to tag all common variants in the 10 genes. The statistical analysis is based on three methods: unconditional logistic regression, multifactor dimensionality reduction and hierarchical cluster analysis. We examined all two- and three-way combinations with unconditional logistic regression and multifactor dimensionality reduction, and used a global approach with all SNPs in the hierarchical cluster analysis. Single-locus studies of an association of genetic variants in the antioxidant defence genes and breast cancer have been contradictory and inconclusive. It is the first time, to our knowledge, the association between multilocus genotypes across genes coding for antioxidant defence enzymes and breast cancer is investigated. We found no evidence of an association with breast cancer with our multilocus approach. The search for two-way interactions gave experiment-wise significance levels of P=0.24 (TXN [t2715c] and TXNRD2 [g23524a]) and P=0.58 (GSR [c39396t] and TXNRD2 [a442g]), for the unconditional logistic regression and multifactor dimensionality reduction, respectively. The experiment-wise significance levels for the three-way interactions were P=0.94 (GPX4 [t2572c], TXN [t2715c] and TXNRD2 [g23524a]) and P=0.29 (GSR [c39396t], TXN [t2715c] and TXNRD2 [a442g]) for the unconditional logistic regression and multifactor dimensionality reduction, respectively. In the hierarchical cluster analysis neither the average across four rounds with replacement of missing values at random (P=0.12) nor a fifth round with more balanced proportion of missing values between cases and controls (P=0.17) was significant

Comparison of self-reported physical activity between survivors of out-of-hospital cardiac arrest and patients with myocardial infarction without cardiac arrest: a case-control study

Aims To investigate whether out-of-hospital cardiac arrest (OHCA) survivors had lower levels of self-reported physical activity compared to a non-cardiac arrest control group with myocardial infarction (MI), and to explore if symptoms of anxiety, depression, kinesiophobia (fear of movement) and fatigue were associated with a low level of physical activity. Methods Predefined case–control sub-study within the international Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. OHCA survivors at 8 of 61 TTM2 sites in Sweden, Denmark and the United Kingdom were invited. Participants were matched 1:1 to MI controls. Both OHCA survivors and MI controls answered two questions on self-reported physical activity, categorized as a low, moderate, or high level of physical activity, and questionnaires on anxiety and depression symptoms, kinesiophobia, and fatigue 7 months after the cardiac event. Results Overall, 106 of 184 (58%) eligible OHCA survivors were included and matched to 91 MI controls. In total, 25% of OHCA survivors and 20% of MI controls reported a low level of physical activity, with no significant difference (p=0.13). Symptoms of kinesiophobia and fatigue were significantly associated with a low level of physical activity in both groups. OHCA survivors had significantly more kinesiophobia compared to MI controls (18% versus 9%, p=0.04), while levels of anxiety and depression symptoms and fatigue were similar. Conclusion OHCA survivors had similar levels of physical activity compared to matched MI controls. High level of kinesiophobia and fatigue were associated with a low level of physical activity in both groups

Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management

Aromatase inhibitors are widely used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. While the agents are associated with slightly improved survival outcomes when compared to tamoxifen alone, bone and musculoskeletal side effects are substantial and often lead to discontinuation of therapy. Ideally, the symptoms should be prevented or adequately treated. This review will focus on bone and musculoskeletal side effects of aromatase inhibitors, including osteoporosis, fractures, and arthralgias. Recent advances have been made in identifying potential mechanisms underlying these effects. Adequate management of symptoms may enhance patient adherence to therapy, thereby improving breast cancer-related outcomes