Reinforcing informed medication prescription for low back pain in the emergency department (RIME): a controlled interrupted time series implementation study protocol.

INTRODUCTION: Management guidelines for low back pain (LBP) recommend exclusion of serious pathology, followed by simple analgesics, superficial heat therapy, early mobilisation and patient education. An audit in a large metropolitan hospital emergency department (ED) revealed high rates of non-recommended medication prescription for LBP (65% of patients prescribed opioids, 17% prescribed benzodiazepines), high inpatient admission rates (20% of ED LBP patients), delayed patient mobilisation (on average 6 hours) and inadequate patient education (48% of patients). This study aims to improve medication prescription for LBP in this ED by implementing an intervention shown previously to improve guideline-based management of LBP in other Australian EDs. METHODS AND ANALYSIS: A controlled interrupted time series study will evaluate the intervention in the ED before (24 weeks; 20 March 2023-3 September 2023) and after (24 weeks; 27 November 2024-12 May 2024) implementation (12 weeks; 4 September 2023-26 November 2023), additionally comparing findings with another ED in the same health service. The multicomponent implementation strategy uses a formalised clinical flow chart to support clinical decision-making and aims to change clinician behaviour, through clinician education, provision of alternative treatments, educational resources, audit and feedback, supported by implementation champions. The primary outcome is the percentage of LBP patients prescribed non-recommended medications (opioids, benzodiazepines and/or gabapentinoids), assessed via routinely collected ED data. Anticipated sample size is 2000 patients (n=1000 intervention, n=1000 control) based on average monthly admissions of LBP presentations in the EDs. Secondary outcomes include inpatient admission rate, time to mobilisation, provision of patient education, imaging requests, representation to the ED within 6 months and healthcare costs. In nested qualitative research, we will study ED clinicians' perceptions of the implementation and identify how benefits can be sustained over time. ETHICS AND DISSEMINATION: This study received ethical approval from the Metro North Human Research Ethics Committee (HREC/2022/MNHA/87995). Study findings will be published in peer-reviewed journals and presented at international conferences and educational workshops. TRIAL REGISTRATION NUMBER: ACTRN12622001536752.

Long-Term Outcomes of Dose-Escalated Pelvic Lymph Node Intensity-Modulated Radiation Therapy (IMRT) With a Simultaneous Hypofractionated Boost to the Prostate for Very High-Risk Adenocarcinoma of the Prostate: A Prospective Phase II Clinical Trial.

PURPOSE: There remains limited data as to the feasibility, safety, and efficacy of higher doses of elective radiation therapy to the pelvic lymph nodes in men with high-risk prostate cancer. We conducted a phase II study to evaluate moderate dose escalation to the pelvic lymph nodes using a simultaneous integrated boost to the prostate. METHODS AND MATERIALS: Patients were eligible with biopsy-proven adenocarcinoma of the prostate, a calculated lymph node risk of at least 25%, Karnofsky performance scale ≥70, and no evidence of M1 disease. Acute and late toxicity were prospectively collected at each follow-up using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). The pelvic lymph nodes were treated to a dose of 56 Gy over 28 fractions with a simultaneous integrated boost to the prostate to a total dose of 70 Gy over 28 fractions using intensity-modulated radiation therapy. RESULTS: Thirty patients were prospectively enrolled from October 2010 to August 2014. Median patient age was 70 years (57-83), pretreatment prostate-specific antigen was 11.5 ng/mL (3.23-111.5), T stage was T2c (T1c-T3b), and Gleason score was 9 (6-9). CTCAE v4.0 rate of any grade 1 or 2 genitourinary and gastrointestinal toxicity were 55% and 44%, respectively, and there was 1 reported acute grade 3 genitourinary and gastrointestinal toxicity, both unrelated to protocol therapy. With a median follow-up of 6.4 years, the biochemical failure free survival rate was 80.2%, and mean biochemical progression free survival was 8.3 years (95% confidence interval [CI], 7.2-9.4). The prostate cancer specific survival was 95.2%, and mean prostate cancer specific survival was 8.7 years (95% CI, 8.0-9.4). Five-year distant metastases free survival was 96%. Medians were not reached. CONCLUSIONS: In this single arm, small, prospective feasibility study, nodal radiation therapy dose escalation was safe, feasible, and seemingly well tolerated. Rates of progression free survival are highly encouraging in this population of predominately National Comprehensive Cancer Network very high-risk patients.

Phase II open label, multi-center clinical trial of modulation of intermediate endpoint biomarkers by 1α-hydroxyvitamin D2 in patients with clinically localized prostate cancer and high grade pin.

BACKGROUND: Prostate cancer is the most common malignancy and second leading cause of cancer related deaths in American men supporting the study of prostate cancer chemoprevention. Major risk factors for this disease have been associated with low serum levels of vitamin D. Here, we evaluate the biologic activity of a less calcemic vitamin D analog 1α-hydroxyvitamin D2 [1α-OH-D2] (Bone Care International, Inc.) in patients with prostate cancer and high grade prostatic intraepithelial neoplasia (HG PIN). METHODS: Patients with clinically organ-confined prostate cancer and HG PIN were randomized to 1α-OH-D2 versus placebo for 28 days prior to radical prostatectomy. Intermediate endpoint biomarkers included serum vitamin D metabolites, TGFß 1/2, free/total PSA, IGF-1, IGFBP-3, bFGF, and VEGF. Tissue endpoints included histology, MIB-1 and TUNEL staining, microvessel density and factor VIII staining, androgen receptor and PSA, vitamin D receptor expression and nuclear morphometry. RESULTS: The 1α-OH-D2 vitamin D analog was well tolerated and could be safely administered with good compliance and no evidence of hypercalcemia over 28 days. While serum vitamin D metabolite levels only slightly increased, evidence of biologic activity was observed with significant reductions in serum PTH levels. TGF-ß2 was the only biomarker significantly altered by vitamin D supplementation. Whether reduced TGF-ß2 levels in our study is an early indicator of response to vitamin D remains unclear. CONCLUSIONS: While further investigation of vitamin D may be warranted based on preclinical studies, results of the present trial do not appear to justify evaluation of 1α-OH-D2 in larger clinical prostate cancer prevention studies.

Adjuvant hormone therapy after radiation or surgery for localized or locally advanced prostate cancer.

Prostate cancer is being diagnosed at an earlier age and earlier disease stage than previously and increasing numbers of relatively young men are receiving potentially curative radical prostatectomy or radiotherapy for early prostate cancer. Although many of these men have an excellent outcome, a significant proportion subsequently experience disease recurrence or cancer-related death. Men with unfavorable tumor characteristics at the time of radical prostatectomy or radiotherapy are particularly at high risk of experiencing disease recurrence. One strategy to improve outcome for these men is adjuvant hormone therapy (hormone therapy administered immediately after therapy of primary curative intent). Surgical castration (bilateral orchiectomy), medical castration using the luteinizing hormone-releasing hormone (LHRH) agonist goserelin, and antiandrogen monotherapy have been investigated as adjuvant hormone therapy to radical prostatectomy and radiotherapy, and each therapy has demonstrated clinical benefits because of a significant improvement in disease-free survival. Furthermore, data are available to indicate that adjuvant hormone therapy achieved by goserelin or bilateral orchiectomy improves overall survival, particularly in men at high risk of progression. Because the effects of LHRH agonists are reversible, they provide a more acceptable method of adjuvant therapy compared to bilateral orchiectomy, particularly in the adjuvant setting, and are preferred by patients. However, the adverse effects on quality of life, in particular on sexual interest and function and bone mineral density, may limit the use of LHRH agonists in some patients. However, these parameters are maintained with nonsteroidal antiandrogens. The first data from the Early Prostate Cancer program indicate that adjuvant bicalutamide 150 mg is associated with a significant improvement in progression-free survival after radical prostatectomy or radiotherapy. Gynecomastia and breast pain are the most common side effects associated with bicalutamide therapy. Medical or surgical castration in combination with an antiandrogen (combined androgen blockade) is another option for use as an adjuvant hormone therapy. However, no study has reported on the use of combined androgen blockade in this setting. Adjuvant hormone therapy provides clinicians with another treatment option for patients with early prostate cancer and unfavorable tumor characteristics.