Background
Chronic pain is frequent in persons living with spinal cord injury (SCI). Conventionally, the pain is treated pharmacologically, yet long‐term pain medication is often refractory and ...associated with side effects. Non‐pharmacological interventions are frequently advocated, although the benefit and harm profiles of these treatments are not well established, in part because of methodological weaknesses of available studies.
Objectives
To critically appraise and synthesise available research evidence on the effects of non‐pharmacological interventions for the treatment of chronic neuropathic and nociceptive pain in people living with SCI.
Search methods
The search was run on the 1st March 2011. We searched the Cochrane Injuries Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), four other databases and clinical trials registers. In addition, we manually searched the proceedings of three major scientific conferences on SCI. We updated this search in November 2014 but these results have not yet been incorporated.
Selection criteria
Randomised controlled trials of any intervention not involving intake of medication or other active substances to treat chronic pain in people with SCI.
Data collection and analysis
Two review authors independently extracted data and assessed risk of bias in the included studies. The primary outcome was any measure of pain intensity or pain relief. Secondary outcomes included adverse events, anxiety, depression and quality of life. When possible, meta‐analyses were performed to calculate standardised mean differences for each type of intervention.
Main results
We identified 16 trials involving a total of 616 participants. Eight different types of interventions were studied. Eight trials investigated the effects of electrical brain stimulation (transcranial direct current stimulation (tDCS) and cranial electrotherapy stimulation (CES); five trials) or repetitive transcranial magnetic stimulation (rTMS; three trials). Interventions in the remaining studies included exercise programmes (three trials); acupuncture (two trials); self‐hypnosis (one trial); transcutaneous electrical nerve stimulation (TENS) (one trial); and a cognitive behavioural programme (one trial). None of the included trials were considered to have low overall risk of bias. Twelve studies had high overall risk of bias, and in four studies risk of bias was unclear. The overall quality of the included studies was weak. Their validity was impaired by methodological weaknesses such as inappropriate choice of control groups. An additional search in November 2014 identified more recent studies that will be included in an update of this review.
For tDCS the pooled mean difference between intervention and control groups in pain scores on an 11‐point visual analogue scale (VAS) (0‐10) was a reduction of ‐1.90 units (95% confidence interval (CI) ‐3.48 to ‐0.33; P value 0.02) in the short term and of ‐1.87 (95% CI ‐3.30 to ‐0.45; P value 0.01) in the mid term. Exercise programmes led to mean reductions in chronic shoulder pain of ‐1.9 score points for the Short Form (SF)‐36 item for pain experience (95% CI ‐3.4 to ‐0.4; P value 0.01) and ‐2.8 pain VAS units (95% CI ‐3.77 to ‐1.83; P value < 0.00001); this represented the largest observed treatment effects in the included studies. Trials using rTMS, CES, acupuncture, self‐hypnosis, TENS or a cognitive behavioural programme provided no evidence that these interventions reduce chronic pain. Ten trials examined study endpoints other than pain, including anxiety, depression and quality of life, but available data were too scarce for firm conclusions to be drawn. In four trials no side effects were reported with study interventions. Five trials reported transient mild side effects. Overall, a paucity of evidence was found on any serious or long‐lasting side effects of the interventions.
Authors' conclusions
Evidence is insufficient to suggest that non‐pharmacological treatments are effective in reducing chronic pain in people living with SCI. The benefits and harms of commonly used non‐pharmacological pain treatments should be investigated in randomised controlled trials with adequate sample size and study methodology.
Neuroinflammation is a physiological response aimed at maintaining the homodynamic balance and providing the body with the fundamental resource of adaptation to endogenous and exogenous stimuli. ...Although the response is initiated with protective purposes, the effect may be detrimental when not regulated. The physiological control of neuroinflammation is mainly achieved via regulatory mechanisms performed by particular cells of the immune system intimately associated with or within the nervous system and named "non-neuronal cells." In particular, mast cells (within the central nervous system and in the periphery) and microglia (at spinal and supraspinal level) are involved in this control, through a close functional relationship between them and neurons (either centrally, spinal, or peripherally located). Accordingly, neuroinflammation becomes a worsening factor in many disorders whenever the non-neuronal cell supervision is inadequate. It has been shown that the regulation of non-neuronal cells-and therefore the control of neuroinflammation-depends on the local "
" synthesis of the endogenous lipid amide Palmitoylethanolamide and related endocannabinoids. When the balance between synthesis and degradation of this bioactive lipid mediator is disrupted in favor of reduced synthesis and/or increased degradation, the behavior of non-neuronal cells may not be appropriately regulated and neuroinflammation exceeds the physiological boundaries. In these conditions, it has been demonstrated that the increase of endogenous Palmitoylethanolamide-either by decreasing its degradation or exogenous administration-is able to keep neuroinflammation within its physiological limits. In this review the large number of studies on the benefits derived from oral administration of micronized and highly bioavailable forms of Palmitoylethanolamide is discussed, with special reference to neuroinflammatory disorders.
Profiling candidate therapeutics with limited cancer models during preclinical development hinders predictions of clinical efficacy and identifying factors that underlie heterogeneous patient ...responses for patient-selection strategies. We established ∼1,000 patient-derived tumor xenograft models (PDXs) with a diverse set of driver mutations. With these PDXs, we performed in vivo compound screens using a 1 × 1 × 1 experimental design (PDX clinical trial or PCT) to assess the population responses to 62 treatments across six indications. We demonstrate both the reproducibility and the clinical translatability of this approach by identifying associations between a genotype and drug response, and established mechanisms of resistance. In addition, our results suggest that PCTs may represent a more accurate approach than cell line models for assessing the clinical potential of some therapeutic modalities. We therefore propose that this experimental paradigm could potentially improve preclinical evaluation of treatment modalities and enhance our ability to predict clinical trial responses.
This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.
A multidisciplinary panel conducted pragmatic systematic ...reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.
The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions.
The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.
Stem cell-based approaches have received much hype as potential treatments for neurodegenerative disorders. Indeed, transplantation of stem cells or their derivatives in animal models of ...neurodegenerative diseases can improve function by replacing the lost neurons and glial cells and by mediating remyelination, trophic actions, and modulation of inflammation. Endogenous neural stem cells are also potential therapeutic targets because they produce neurons and glial cells in response to injury and could be affected by the degenerative process. As we discuss here, however, significant hurdles remain before these findings can be responsibly translated to novel therapies. In particular, we need to better understand the mechanisms of action of stem cells after transplantation and learn how to control stem cell proliferation, survival, migration, and differentiation in the pathological environment.
Lung cancer is the primary cause of mortality in the United States and around the globe. Therapeutic options for lung cancer treatment include surgery, radiation therapy, chemotherapy, and targeted ...drug therapy. Medical management is often associated with the development of treatment resistance leading to relapse. Immunotherapy is profoundly altering the approach to cancer treatment owing to its tolerable safety profile, sustained therapeutic response due to immunological memory generation, and effectiveness across a broad patient population. Different tumor-specific vaccination strategies are gaining ground in the treatment of lung cancer. Recent advances in adoptive cell therapy (CAR T, TCR, TIL), the associated clinical trials on lung cancer, and associated hurdles are discussed in this review. Recent trials on lung cancer patients (without a targetable oncogenic driver alteration) reveal significant and sustained responses when treated with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint blockade immunotherapies. Accumulating evidence indicates that a loss of effective anti-tumor immunity is associated with lung tumor evolution. Therapeutic cancer vaccines combined with immune checkpoint inhibitors (ICI) can achieve better therapeutic effects. To this end, the present article encompasses a detailed overview of the recent developments in the immunotherapeutic landscape in targeting small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Additionally, the review also explores the implication of nanomedicine in lung cancer immunotherapy as well as the combinatorial application of traditional therapy along with immunotherapy regimens. Finally, ongoing clinical trials, significant obstacles, and the future outlook of this treatment strategy are also highlighted to boost further research in the field.
Hepatocellular carcinoma (HCC) is an aggressive liver tumor with a poor 5-year survival rate. Many HCCs are not amenable to surgical resection, because of tumor size, location, or because of the ...patient's poor liver function, a common obstacle to HCC therapy, because HCCs almost always develop in chronically inflamed livers.
In recent years, many efforts have been made to improve patient survival by conducting clinical trials investigating local and systemic treatment options for patients with unresectable tumors. These treatment options include radiofrequency ablation (RFA), transarterial chemoembolization (TACE), selective internal radiotherapy with yttrium-90 (SIRT), stereotactic body radiation therapy (SBRT), proton beam therapy, molecular targeted therapy, and checkpoint inhibition. In this "to-the-point" article, we review the current standard and summarize the most recent findings in unresectable HCC treatment.
(1) RFA is currently the preferred treatment for patients with tumor burden restricted to the liver and not eligible for surgical resection; (2) TACE is utilized in patients who are not eligible for RFA because of tumor location and/or number of tumor lesions; (3) SIRT might improve treatment responses achieved by TACE and is feasible in patients with portal vein thrombosis; (4) new radiation therapy treatment modalities such as SBRT and proton beam therapy show promising results for local tumor control; and (5) sorafenib remains the first-line systemic treatment option after several large clinical trials have failed to show superiority of other molecular targeted therapies in HCC patients.
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