Pain outcomes in patients with bone metastases from advanced cancer: assessment and management with bone-targeting agents

Bone metastases in advanced cancer frequently cause painful complications that impair patient physical activity and negatively affect quality of life. Pain is often underreported and poorly managed in these patients. The most commonly used pain assessment instruments are visual analogue scales, a single-item measure, and the Brief Pain Inventory Questionnaire-Short Form. The World Health Organization analgesic ladder and the Analgesic Quantification Algorithm are used to evaluate analgesic use. Bone-targeting agents, such as denosumab or bisphosphonates, prevent skeletal complications (i.e., radiation to bone, pathologic fractures, surgery to bone, and spinal cord compression) and can also improve pain outcomes in patients with metastatic bone disease. We have reviewed pain outcomes and analgesic use and reported pain data from an integrated analysis of randomized controlled studies of denosumab versus the bisphosphonate zoledronic acid (ZA) in patients with bone metastases from advanced solid tumors. Intravenous bisphosphonates improved pain outcomes in patients with bone metastases from solid tumors. Compared with ZA, denosumab further prevented pain worsening and delayed the need for treatment with strong opioids. In patients with no or mild pain at baseline, denosumab reduced the risk of increasing pain severity and delayed pain worsening along with the time to increased pain interference compared with ZA, suggesting that use of denosumab (with appropriate calcium and vitamin D supplementation) before patients develop bone pain may improve outcomes. These data also support the use of validated pain assessments to optimize treatment and reduce the burden of pain associated with metastatic bone disease

Incidence, severity, aetiology and type of neck injury in men's amateur rugby union: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>There is a paucity of epidemiological data on neck injury in amateur rugby union populations. The objective of this study was to determine the incidence, severity, aetiology and type of neck injury in Australian men's amateur rugby union.</p> <p>Methods</p> <p>Data was collected from a cohort of 262 participants from two Australian amateur men's rugby union clubs via a prospective cohort study design. A modified version of the Rugby Union Injury Report Form for Games and Training was used by the clubs physiotherapist or chiropractor in data collection.</p> <p>Results</p> <p>The participants sustained 90 (eight recurrent) neck injuries. Exposure time was calculated at 31143.8 hours of play (12863.8 hours of match time and 18280 hours of training). Incidence of neck injury was 2.9 injuries/1000 player-hours (95%CI: 2.3, 3.6). As a consequence 69.3% neck injuries were minor, 17% mild, 6.8% moderate and 6.8% severe. Neck compression was the most frequent aetiology and was weakly associated with severity. Cervical facet injury was the most frequent neck injury type.</p> <p>Conclusions</p> <p>This is the first prospective cohort study in an amateur men's rugby union population since the inception of professionalism that presents injury rate, severity, aetiology and injury type data for neck injury. Current epidemiological data should be sought when evaluating the risks associated with rugby union football.</p

Genomic analysis of Pseudomonas putida: genes in a genome island are crucial for nicotine degradation

Nicotine is an important chemical compound in nature that has been regarded as an environmental toxicant causing various preventable diseases. Several bacterial species are adapted to decompose this heterocyclic compound, including Pseudomonas and Arthrobacter. Pseudomonas putida S16 is a bacterium that degrades nicotine through the pyrrolidine pathway, similar to that present in animals. The corresponding late steps of the nicotine degradation pathway in P. putida S16 was first proposed and demonstrated to be from 2,5-dihydroxy-pyridine through the intermediates N-formylmaleamic acid, maleamic acid, maleic acid, and fumaric acid. Genomics of strain S16 revealed that genes located in the largest genome island play a major role in nicotine degradation and may originate from other strains, as suggested by the constructed phylogenetic tree and the results of comparative genomic analysis. The deletion of gene hpo showed that this gene is essential for nicotine degradation. This study defines the mechanism of nicotine degradation

Fixation of osteochondral fragments in the human knee using Meniscus Arrows®

The aim of this study is to compare the hold in bone of Meniscus Arrows® and Smart Nails®, followed by the report of the results of the clinical application of Meniscus Arrows® as fixation devices. First, pull-out tests were performed to analyse the holdfast of both nails in bone. Statistical analysis showed no significant difference; therefore, the thinner Meniscus Arrow® was chosen as fixation device in the patient series of two patients with a symptomatic Osteochondritis dissecans fragment and three patients with an osteochondral fracture of a femur condyle. The cartilage margins were glued with Tissuecoll®. All fragments consolidated. Second look arthroscopy in three patients showed fixed fragments with stable, congruent cartilage edges. At an average follow-up period of 5 years no pain, effusion, locking, restricted range of motion or signs of osteoarthritis were reported. Based on the results of the pull-out tests and available clinical studies, Meniscus Arrows® and Smart Nails® are both likely to perform adequately as fixation devices in the treatment of Osteochondritis dissecans and osteochondral fractures in the knee. They both provide the advantage of one stage surgery. However, based on their smaller diameter, the Meniscus Arrows® should be preferred for this indication

CYP17 blockade by abiraterone: further evidence for frequent continued hormone-dependence in castration-resistant prostate cancer

The limited prognosis of patients with castration-resistant prostate cancer (CRPC) on existing hormonal manipulation therapies calls out for the urgent need for new management strategies. The novel, orally available, small-molecule compound, abiraterone acetate, is undergoing evaluation in early clinical trials and emerging data have shown that the selective, irreversible and continuous inhibition of CYP17 is safe with durable responses in CRPC. Importantly, these efficacy data along with strong preclinical evidence indicate that a significant proportion of CRPC remains dependant on ligand-activated androgen receptor (AR) signalling. Coupled with the use of innovative biological molecular techniques, including the characterisation of circulating tumour cells and ETS gene fusion analyses, we have gained insights into the molecular basis of CRPC. We envision that a better understanding of the mechanisms underlying resistance to abiraterone acetate, as well as the development of validated predictive and intermediate endpoint biomarkers to aid both patient selection and monitor response to treatment, will improve the outcome of CRPC patients

Current and Emerging Treatment Options for Castration-Resistant Prostate Cancer: A Focus on Immunotherapy

BACKGROUND: Castration-resistant prostate cancer is a disease with limited treatment options. However, the ongoing elucidation of the mechanisms underlying this disease continues to support the development of not only novel agents, but also innovative approaches. Among these therapies, immunotherapy has emerged as a promising strategy. DESIGN: This review article summarizes the most recent data from investigations of immunotherapies in castration-resistant prostate cancer (literature and congress searches current as of August 2011). RESULTS: Immunotherapeutic strategies such as passive immunization, vaccines, and particularly checkpoint blockade have demonstrated some efficacy as single agents. Elucidation of effective combinations of agents and drug regimens is ongoing but will require continued careful investigation, including the standardization of surrogate endpoints in clinical trials. CONCLUSIONS: It is hypothesized that the combination of immunotherapeutic agents with traditional and novel chemotherapeutics will potentiate the efficacy of the chemotherapeutics while maintaining manageable toxicity

Maternal depressive symptoms, and not anxiety symptoms, are associated with positive mother–child reporting discrepancies of internalizing problems in children: a report on the TRAILS Study

Maternal internalizing problems affect reporting of child’s problem behavior. This study addresses the relative effects of maternal depressive symptoms versus anxiety symptoms and the association with differential reporting of mother and child on child’s internalizing problems. The study sample comprised a cohort of 1,986 10- to 12-year-old children and their mothers from the Dutch general population in a cross sectional setup. Children’s internalizing problems were assessed with the DSM-IV anxiety and affective problem scales of the Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR). Current maternal internalizing problems were assessed with the depressive and anxiety symptom scales of the Depression Anxiety Stress Scale (DASS), while the TRAILS Family History Interview (FHI) measured lifetime maternal depression and anxiety. Results show that current and lifetime maternal depressive symptoms were associated with positive mother–child reporting discrepancies (i.e. mothers reporting more problems than their child). Considering the small amount of variance explained, we conclude that maternal depressive symptoms do not bias maternal reporting on child’s internalizing problems to a serious degree. Studies concerning long term consequences of mother–child reporting discrepancies on child’s internalizing problems are few, but show a risk for adverse outcome. More prognostic research is needed