Music therapy, neural processing, and craving reduction: an RCT protocol for a mixed methods feasibility study in a Community Substance Misuse Treatment Service.

BACKGROUND: Music therapy has been shown to be effective for multiple clinical endpoints associated with substance use disorder such as craving reduction, emotion regulation, depression, and anxiety, but there are a lack of studies investigating those effects in UK Community Substance Misuse Treatment Services (CSMTSs). Furthermore, there is a demand for identifying music therapy mechanisms of change and related brain processes for substance use disorder treatment. The present study aims to evaluate the feasibility and acceptability of music therapy and a pre-test, post-test, and in-session measurement battery in a CSMTS. METHODS: Fifteen participants, from a community service based in London, will take part in a mixed-methods non-blind randomized-controlled trial. Ten participants will receive six-weekly sessions of music therapy in addition to the standard treatment offered by the CSMTS-five of them will receive individual music therapy and five of them will receive group music therapy-while a further five participants will act as a control group receiving standard treatment only. Satisfaction and acceptability will be evaluated in focus groups with service users and staff members following the final treatment session. Moreover, attendance and completion rates will be monitored throughout the intervention. Subjective and behavioral indexes will be assessed before and after the interventions to explore the effects of music therapy on craving, substance use, symptoms of depression and anxiety, inhibitory control, and will be correlated with associated neurophysiological signatures. In-session analysis of two individual music therapy sessions will serve to explore how music and emotion are processed in the brain within the therapy. The data collected at each step will be included in an intention-to-treat analysis basis. DISCUSSION: This study will provide a first report on the feasibility of music therapy as an intervention for participants with substance use disorder engaged within a community service. It will also provide valuable information regarding the implementation of a multifaceted methodology that includes neurophysiological, questionnaire-based, and behavioral assessments in this cohort. Notwithstanding the limitation of a small sample size, the present study will provide novel preliminary data regarding neurophysiological outcomes in participants with substance use disorder that received music therapy. TRIAL REGISTRATION: ClinicalTrails.gov, NCT0518061, Registered 6 January 2022, https://clinicaltrials.gov/ct2/show/NCT05180617.

Neoadjuvant chemotherapy for high-risk prostatic adenocarcinoma.

INTRODUCTION: Neoadjuvant chemotherapy in high-risk, locally advanced prostate cancer remains an understudied area of prostate cancer. Chemotherapy continues to be a viable option. The combination with surgery may be desired but lacks data for complete recommendation. CASE PRESENTATION: We demonstrate the successful utilization of chemotherapy in the neoadjuvant arena. A 70-year-old male was diagnosed with high-risk prostate cancer on biopsy. Upon multiparametric magnetic resonance imaging, the patient had local rectal wall invasion and stage T4 N0 M0 after a negative bone scan. After treatment with androgen-deprivation therapy and docetaxel, repeat multiparametric magnetic resonance imaging showed regression of rectal invasion. The patient elected for prostatectomy and avoided proctectomy and colostomy. The patient's postoperative prostate-specific antigen was undetectable on initial follow-up. CONCLUSION: We show that neoadjuvant chemotherapy merits further study and may provide a more permanent surgical option for patients.

Proteolysis is the most fundamental property of malignancy and its inhibition may be used therapeutically (Review).

The mortality rates of cancer patients decreased by ~1.5% per year between 2001 and 2015, although the decrease depends on patient sex, ethnic group and type of malignancy. Cancer remains a significant global health problem, requiring a search for novel treatments. The most common property of malignant tumors is their capacity to invade adjacent tissue and to metastasize, and this cancer aggressiveness is contingent on overexpression of proteolytic enzymes. The components of the plasminogen activation system (PAS) and the metalloproteinase family [mainly matrix metalloproteinases (MMPs)] are overexpressed in malignant tumors, driving the local invasion, metastasis and angiogenesis. This is the case for numerous types of cancer, such as breast, colon, prostate and oral carcinoma, among others. Present chemotherapeutics agents typically attack all dividing cells; however, for future therapeutic agents to be clinically successful, they need to be highly selective for a specific protein(s) and act on the cancerous tissues without adverse systemic effects. Inhibition of proteolysis in cancerous tissue has the ability to attenuate tumor invasion, angiogenesis and migration. For that purpose, inhibiting both PAS and MMPs may be another approach, since the two groups of enzymes are overexpressed in cancer. In the present review, the roles and new findings on PAS and MMP families in cancer formation, growth and possible treatments are discussed.

A panel of DNA methylation markers reveals extensive methylation in histologically benign prostate biopsy cores from cancer patients.

BACKGROUND: Men with a negative first prostate biopsy will undergo one or more additional biopsies if they remain at high suspicion of prostate cancer. To date, there are no diagnostic tests capable of identifying patients at risk for a positive diagnosis with the predictive power needed to eliminate unnecessary repeat biopsies. Efforts to develop clinical tests using the epigenetic signature of cores recovered from first biopsies have been limited to a few markers and lack the sensitivity and specificity needed for widespread clinical adoption. METHODS: We developed methylation-specific quantitative polymerase chain reaction assays for a panel of 24 markers that are preferentially methylated in prostate cancer. We modified the bisulfite conversion conditions to allow the integration of the methylation information from multiple markers. We determined the methylation status of the 24 markers in 213 prostate biopsy cores from 104 patients, 37 prostate cancer patients and 67 controls. We performed logistic regression on combinations of markers as well as the entire panel of 24 markers to identify the best candidates for a diagnostic test. RESULTS: The marker panel differentiated between cancer cores and benign cores from non-cancer patients with 100% sensitivity and 97% specificity. Furthermore, the panel detected significant methylation in benign cores from prostate cancer patients that was not present in controls. Using methylation of 5 out of 24 to define a cancer case, the analysis of a single benign biopsy core identified 62% of prostate cancer patients undergoing repeat biopsies. ROC curve analysis showed that markers commonly methylated in benign cores from cancer patients are the best candidates for a diagnostic test. The results suggest that 5 to 10 markers will be needed to achieve optimal predictive power. CONCLUSIONS: This study shows that epigenetic field effects differ significantly between cancer patients and controls. Their detection in benign biopsy cores can form the basis of diagnostic tests to identify patients in need of repeat biopsies, reducing the cost of continued PCA screening by up to 40%. They could also be used to identify prostate cancer patients with low grade disease who are likely candidates for active surveillance or focal therapy.

Practice based collaboration to improve the use of immediate intravesical therapy after resection of nonmuscle invasive bladder cancer.

PURPOSE: Perioperative instillation of intravesical chemotherapy after bladder tumor resection is supported by level I evidence showing a 30% decrease in tumor recurrence. However, studies of administrative data sets show poor use in practice. MATERIALS AND METHODS: We prospectively evaluated the use of perioperative intravesical chemotherapy in a multipractice quality improvement collaborative. Cases were categorized as ideal for intravesical chemotherapy (1 or 2 papillary tumors, cTa/cT1 and completely resected) and nonideal. The reasons for not administering intravesical chemotherapy in ideal cases were classified as appropriate or modifiable. Before and after comparative feedback and educational interventions we calculated judicious use of intravesical chemotherapy (nonuse in nonideal cases plus use in ideal cases plus appropriate nonuse in ideal cases) and quality improvement potential (use in nonideal cases plus nonuse in ideal cases attributable to modifiable factors). RESULTS: We accrued a total of 2,794 cases at the 5 sites in 22 months. The rate of use in ideal cases was 38% before and 34.8% after intervention (p=0.36), while use in nonideal cases decreased from 15% to 12% (p=0.08). Overall, intravesical chemotherapy was used judiciously in 83.0% to 85.7% of cases, while the remaining 14.3% to 17.0% represented quality improvement potential. CONCLUSIONS: Judicious use of perioperative intravesical chemotherapy is relatively high in routine practice. Most instances of nonuse represent appropriate clinical judgment. Utilization did not change after quality improvement interventions, suggesting that there may a ceiling effect that makes it difficult to improve care that is high quality at baseline. Moreover, decreasing unnecessary use of an intervention may be easier than encouraging appropriate use of potentially toxic therapy.

Understanding the use of immediate intravesical chemotherapy for patients with bladder cancer.

PURPOSE: Despite its established efficacy in reducing recurrence rates for patients with urothelial carcinoma, immediate intravesical chemotherapy is reportedly used infrequently. Accordingly, the Urological Surgery Quality Collaborative implemented a project aimed at understanding and improving the use of immediate intravesical chemotherapy. MATERIALS AND METHODS: Surgeons in 5 Urological Surgery Quality Collaborative practices prospectively collected clinical and baseline intravesical chemotherapy use data for patients undergoing bladder biopsy or transurethral bladder tumor resection from September 2010 through January 2012. In the second phase of data collection (June 2011 through January 2012) treating surgeons also documented reasons for not administering intravesical chemotherapy. We defined patients with 1 to 2 clinical stage Ta/T1, completely resected, papillary tumor(s) as ideal candidates for treatment with immediate intravesical chemotherapy. For ideal and nonideal patients we examined baseline use of intravesical chemotherapy across Urological Surgery Quality Collaborative practices as well as reasons for not administering therapy among ideal patients. RESULTS: Among 1,931 patients 37.2% met criteria as ideal cases for intravesical chemotherapy administration. We observed significant variation in the use of intravesical chemotherapy across Urological Surgery Quality Collaborative practices for ideal (range 27% to 50%) and nonideal cases (9% to 24%) (p <0.001). Reasons for not treating ideal candidates included lack of confirmation of malignancy (4, 2.8%), uncertainty regarding the benefits of intravesical chemotherapy (28, 19.6%) and logistic factors such as the unavailability of medication (34, 23.8%). CONCLUSIONS: Use of immediate intravesical chemotherapy by Urological Surgery Quality Collaborative practices is higher than reported elsewhere but still varies widely, even among ideal candidates. Efforts to optimize use will be aided by disseminating evidence supporting indications and benefits of intravesical chemotherapy, and by addressing local logistic factors that limit access to this evidence-based therapy.

Human 5-, 12- and 15-lipoxygenase-1 coexist in kidney but show opposite trends and their balance changes in cancer.

Lipoxygenases make an impact on every stage of cancer affecting carcinogenesis, metastasis and apoptosis. While there is a rich literature on individual lipoxygenases we lack extensive data on their coexistence and balance in different organs and types of cancer. Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, characterized by a lack of early warning signs, diverse clinical manifestations, resistance to radiation and chemotherapy. One third of patients will relapse and the 5­year survival rate is <10% in cases of metastases. Many drugs are metabolized in the kidneys and might interact with lipoxygenases that are biocatalysts for many endo- and xenobiotics. In the present study, we examined the kidney tissue from healthy individuals and cancer patients by immunohistochemical analysis for the presence of 3 lipoxygenases: 5-LOX, 12S-LOX and 15-LOX-1. Our findings confirmed their coexistence and opposite trends of manifestation in the course of disease with increased 15-LOX-1 and decreased 5- and 12-LOX levels at the onset of cancer reversing with the progressing stage of the disease or the grade of tumor. Unlike other malignancies, there are no biomarkers to individualize RCC management. Modern therapies are using TKI therapy, targeting VEGF and may cause hypertension as a side-effect. 12S-LOX is intertwined with kinases and VEGF and increased secretion of 12S-HETE in urine is known to accompany hypertension. Thus, it may be valuable to probe 12S-LOX activity and monitor its natural metabolite to seek a possible aid in directing the treatment of patients.

Regional collaboration to improve radiographic staging practices among men with early stage prostate cancer.

PURPOSE: We describe findings from a Urological Surgery Quality Collaborative project focused on improving the use of radiographic staging in men with newly diagnosed prostate cancer. MATERIALS AND METHODS: From May 2009 through September 2010 Urological Surgery Quality Collaborative surgeons collected uniform data for men with newly diagnosed prostate cancer. During this period we implemented 3 phases of data collection. Unlike the baseline phase, the second and third rounds were preceded by collaborative quality improvement interventions, including comparative performance feedback, and review and dissemination of clinical guidelines. We evaluated the use of bone scans and computerized tomography across prostate cancer risk strata, Urological Surgery Quality Collaborative practice locations, and before and after quality improvement interventions. RESULTS: We collected data for 858 men with prostate cancer. Based on the D'Amico classification 44%, 39% and 17% of the men had low, intermediate and high risk cancer, respectively. Overall 25% and 22% of patients underwent staging with a bone scan or computerized tomography, respectively, ordered by a Urological Surgery Quality Collaborative urologist. Urological Surgery Quality Collaborative practices differed significantly in their baseline use of bone scans and computerized tomography for men with low and intermediate risk cancer (p<0.01). Compared with baseline practice patterns (31% bone scans, 28% computerized tomography), urologists in Urological Surgery Quality Collaborative practices ordered fewer bone and computerized tomography scans in post-intervention phases 2 (23%, 21%) and 3 (16%, 13%) of data collection (p<0.01), including a significant reduction in the use of these studies in patients with low and intermediate risk cancer (p<0.05). CONCLUSIONS: Following collaborative feedback on baseline use and review of clinical guidelines, urologists in Urological Surgery Quality Collaborative practices dramatically reduced variations in practice patterns and improved adherence with recommended staging practices.

Establishment of a urological surgery quality collaborative.

PURPOSE: We describe the establishment of the Urological Surgery Quality Collaborative including our pilot project to improve radiographic staging for men with prostate cancer. MATERIALS AND METHODS: The Urological Surgery Quality Collaborative comprises more than 60 urologists from 3 group practices. From May through September 2009 Urological Surgery Quality Collaborative surgeons collected a uniform set of data (eg prostate specific antigen, clinical stage) for men with newly diagnosed prostate cancer. After categorizing the cancer of each patient as low, intermediate or high risk, we analyzed baseline use of staging studies across prostate cancer risk strata and Urological Surgery Quality Collaborative practice locations. RESULTS: Of 215 men with prostate cancer 34%, 42% and 24% had low, intermediate and high risk cancer, respectively. Overall 44% and 43% of patients underwent staging with a bone scan or computerized tomography, respectively, and only 9% and 7% of these studies, respectively, were positive for metastases. Use of staging studies increased across risk strata as bone scans or computerized tomography were performed in 17% and 18%, 41% and 40%, and 88% and 86% of patients, respectively, with low, intermediate and high risk tumors (p<0.01). For men with low risk prostate cancer the use of bone scans and computerized tomography differed significantly across Urological Surgery Quality Collaborative practices (p<0.01) and for this group only 1 bone scan (and no computerized tomography) was positive for metastases. CONCLUSIONS: Use of staging evaluations varies by prostate cancer risk strata and across Urological Surgery Quality Collaborative practices. By feeding these data back to surgeons we may be able to improve practice patterns and avoid unnecessary studies in low risk patients. Attainment of this goal would establish the Urological Surgery Quality Collaborative as a viable infrastructure for collaborative quality improvement in urology.

Prostatic involution after intraprostatic injection of cobra toxin.

PURPOSE: We evaluated the comparative effects of intraprostatic injection of cobra cardiotoxin D and botulinum toxin type A on prostate structure in the rat model. MATERIALS AND METHODS: A total of 18 Sprague-Dawley® rats weighing 500 to 600 gm received a single 0.1 ml injection of saline (6), botulinum toxin type A (6) or the cardiotoxin D (6) component of cobra (Naja naja atra) toxin in the right and left ventral lobes of the prostate. At 14 days the rats were sacrificed. The prostate glands were harvested, weighed and processed for immunohistochemical and morphological studies. RESULTS: Prostate glands injected with cardiotoxin D showed significantly decreased weight compared to that of prostates injected with botulinum toxin type A and the saline control. Prostatic atrophy in the glandular component with flattening of the epithelial lining was seen histologically in rats that received botulinum toxin and cardiotoxin D. Each group injected with cardiotoxin D and botulinum toxin showed a significant increase in the number of apoptotic cells compared with controls while only the botulinum toxin group showed a significant increase in the number of proliferating cells. Only rats injected with botulinum toxin had body weight loss. CONCLUSIONS: Our study shows that intraprostatic injection of cobra cardiotoxin D induces prostatic atrophy and leads to a decrease in prostatic weight greater than that of intraprostatic injection of botulinum toxin type A. No systemic effects, such as decreased body weight, were noted after cardiotoxin D injection. Further studies are warranted but the statistically significant decrease in the number of proliferating cells implies a prolonged effect of cardiotoxin D.

Effect of a behavioral nursing intervention on long-term lipid regulation.

Reduction of dietary fat intake and increased physical activity are first-line interventions for elevated total serum cholesterol (TC) and low-density lipoprotein (LDL) serum cholesterol, which are major and modifiable risk factors for coronary heart disease. This retrospective study reports on the effects of a nurse-managed behavioral intervention (NMBI) program on TC and LDL levels in hyperlipidemic patients. Survival analysis indicated that NMBI patients had a significantly higher probability of attaining normal TC and LDL levels than did patients who received only standard nursing care. Additional analysis showed that actual TC and LDL values declined significantly across the study period with marginally significant group by time interactions. These findings provide preliminary evidence of the effectiveness of the behavioral intervention program with hyperlipidemic patients.