Pre-operative oral nutritional supplementation with dietary advice versus dietary advice alone in weight-losing patients with colorectal cancer: single-blind randomized controlled trial.

BACKGROUND: Pre-operative weight loss has been consistently associated with increased post-operative morbidity. The study aims to determine if pre-operative oral nutritional supplements (ONSs) with dietary advice reduce post-operative complications. METHODS: Single-blinded randomized controlled trial. People with colorectal cancer scheduled for surgery with pre-operative weight loss >1 kg/3-6 months were randomized by using stratified blocks (1:1 ratio) in six hospitals (1 November 2013-28 February 2015). Intervention group was given 250 mL/day ONS (10.1 KJ and 0.096 g protein per mL) and dietary advice. Control group received dietary advice alone. Oral nutritional supplements were administered from diagnosis to the day preceding surgery. Research team was masked to group allocation. Primary outcome was patients with one or more surgical site infection (SSI) or chest infection; secondary outcomes included percentage weight loss, total complications, and body composition measurements. Intention-to-treat analysis was performed with both unadjusted and adjusted analyses. A sample size of 88 was required. RESULTS: Of 101 participants, (55 ONS, 46 controls) 97 had surgery. In intention-to-treat analysis, there were 21/45 (47%) patients with an infection-either an SSI or chest infection in the control group vs. 17/55 (30%) in the ONS group. The odds ratio of a patient incurring either an SSI or chest infection was 0.532 (P = 0.135 confidence interval 0.232 to 1.218) in the unadjusted analysis and when adjusted for random differences at baseline (age, gender, percentage weight loss, and cancer staging) was 0.341 (P = 0.031, confidence interval 0.128 to 0.909). Pre-operative percentage weight loss at the first time point after randomization was 4.1% [interquartile range (IQR) 1.7-7.0] in ONS group vs. 6.7% (IQR 2.6-10.8) in controls (Mann-Whitney U P = 0.021) and post-operatively was 7.4% (IQR 4.3-10.0) in ONS group vs. 10.2% (IQR 5.1-18.5) in controls (P = 0.016). CONCLUSIONS: Compared with dietary advice alone, ONS resulted in patients having fewer infections and less weight loss following surgery for colorectal cancer. We have demonstrated that pre-operative oral nutritional supplementation can improve clinical outcome in weight losing patients with colorectal cancer

Identifying factors likely to influence compliance with diagnostic imaging guideline recommendations for spine disorders among chiropractors in North America: a focus group study using the Theoretical Domains Framework

Background: The Theoretical Domains Framework (TDF) was developed to investigate determinants of specific clinical behaviors and inform the design of interventions to change professional behavior. This framework was used to explore the beliefs of chiropractors in an American Provider Network and two Canadian provinces about their adherence to evidence-based recommendations for spine radiography for uncomplicated back pain. The primary objective of the study was to identify chiropractors’ beliefs about managing uncomplicated back pain without xrays and to explore barriers and facilitators to implementing evidence-based recommendations on lumbar spine xrays. A secondary objective was to compare chiropractors in the United States and Canada on their beliefs regarding the use of spine x-rays. Methods: Six focus groups exploring beliefs about managing back pain without x-rays were conducted with a purposive sample. The interview guide was based upon the TDF. Focus groups were digitally recorded, transcribed verbatim, and analyzed by two independent assessors using thematic content analysis based on the TDF. Results: Five domains were identified as likely relevant. Key beliefs within these domains included the following: conflicting comments about the potential consequences of not ordering x-rays (risk of missing a pathology, avoiding adverse treatment effects, risks of litigation, determining the treatment plan, and using x-ray-driven techniques contrasted with perceived benefits of minimizing patient radiation exposure and reducing costs; beliefs about consequences); beliefs regarding professional autonomy, professional credibility, lack of standardization, and agreement with guidelines widely varied (social/professional role & identity); the influence of formal training, colleagues, and patients also appeared to be important factors (social influences); conflicting comments regarding levels of confidence and comfort in managing patients without x-rays (belief about capabilities); and guideline awareness and agreements (knowledge). Conclusions: Chiropractors’ use of diagnostic imaging appears to be influenced by a number of factors. Five key domains may be important considering the presence of conflicting beliefs, evidence of strong beliefs likely to impact the behavior of interest, and high frequency of beliefs. The results will inform the development of a theorybased survey to help identify potential targets for behavioral-change strategies

A Validated Model to Predict Severe Weight Loss in Amyotrophic Lateral Sclerosis

Severe weight loss in amyotrophic lateral sclerosis (ALS) is common, multifactorial, and associated with shortened survival. Using longitudinal weight data from over 6000 patients with ALS across three cohorts, we built an accelerated failure time model to predict the risk of future severe (≥ 10%) weight loss using five single‐timepoint clinical predictors: symptom duration, revised ALS Functional Rating Scale, site of onset, forced vital capacity, and age. Model performance and generalisability were evaluated using internal–external cross‐validation and random‐effects meta‐analysis. The overall concordance statistic was 0.71 (95% CI 0.63–0.79), and the calibration slope and intercept were 0.91 (0.69–1.13) and 0.05 (−0.11–0.21). This study highlights clinical factors most associated with severe weight loss in ALS and provides the basis for a stratification tool

Enhancing Longitudinal Clinical Trial Efficiency with Digital Twins and Prognostic Covariate-Adjusted Mixed Models for Repeated Measures (PROCOVA-MMRM)

Clinical trials are critical in advancing medical treatments but often suffer from immense time and financial burden. Advances in statistical methodologies and artificial intelligence (AI) present opportunities to address these inefficiencies. Here we introduce Prognostic Covariate-Adjusted Mixed Models for Repeated Measures (PROCOVA-MMRM) as an advantageous combination of prognostic covariate adjustment (PROCOVA) and Mixed Models for Repeated Measures (MMRM). PROCOVA-MMRM utilizes time-matched prognostic scores generated from AI models to enhance the precision of treatment effect estimators for longitudinal continuous outcomes, enabling reductions in sample size and enrollment times. We first provide a description of the background and implementation of PROCOVA-MMRM, followed by two case study reanalyses where we compare the performance of PROCOVA-MMRM versus the unadjusted MMRM. These reanalyses demonstrate significant improvements in statistical power and precision in clinical indications with unmet medical need, specifically Alzheimer's Disease (AD) and Amyotrophic Lateral Sclerosis (ALS). We also explore the potential for sample size reduction with the prospective implementation of PROCOVA-MMRM, finding that the same or better results could have been achieved with fewer participants in these historical trials if the enhanced precision provided by PROCOVA-MMRM had been prospectively leveraged. We also confirm the robustness of the statistical properties of PROCOVA-MMRM in a variety of realistic simulation scenarios. Altogether, PROCOVA-MMRM represents a rigorous method of incorporating advances in the prediction of time-matched prognostic scores generated by AI into longitudinal analysis, potentially reducing both the cost and time required to bring new treatments to patients while adhering to regulatory standards.Comment: 29 pages, 9 table

Laparoscopic versus open colectomy for colon cancer in an older population: a cohort study

<p>Abstract</p> <p>Background</p> <p>Laparoscopic colectomy for colon cancer has been compared with open colectomy in randomized controlled trials, but these studies may not be generalizable because of strict enrollment and exclusion criteria which may explicitly or inadvertently exclude older individuals due to associated comorbidities. Previous studies of older patients undergoing laparoscopic colectomy have generally focused on short-term outcomes. The goals of this cohort study were to identify predictors of laparoscopic colectomy in an older population in the United States and to compare short-term and long-term outcomes.</p> <p>Methods</p> <p>Patients aged 65 years or older with incident colorectal cancer diagnosed 1996-2002 who underwent colectomy within 6 months of cancer diagnosis were identified from the linked Surveillance, Epidemiology, and End Results-Medicare database. Laparoscopic and open colectomy patients were compared with respect to length of stay, blood transfusion requirements, intensive care unit monitoring, complications, 30-day mortality, and long-term survival. We adjusted for potential selection bias in surgical approach with propensity score matching.</p> <p>Results</p> <p>Laparoscopic colectomy cases were associated with left-sided tumors; areas with higher population density, income, and education level; areas in the western United States; and National Cancer Institute-designated cancer centers. Laparoscopic colectomy cases had shorter length of stay and less intensive care unit monitoring. Although laparoscopic colectomy patients (n = 424) had fewer complications (21.5% versus 26.3%), lower 30-day mortality (3.3% versus 5.8%), and longer median survival (6.6 versus 4.8 years) compared with open colectomy patients (n = 27,012), after propensity score matching these differences disappeared.</p> <p>Conclusions</p> <p>In this older population, laparoscopic colectomy practice patterns were associated with factors which likely correlate with tertiary referral centers. Although short-term and long-term survival are comparable, laparoscopic colectomy offers shorter hospitalizations and less intensive care.</p

Optimal Total Mesorectal Excision for Rectal Cancer: the Role of Robotic Surgery from an Expert's View

Total mesorectal excision (TME) has gained worldwide acceptance as a standard surgical technique in the treatment of rectal cancer. Ever since laparoscopic surgery was first applied to TME for rectal cancer, with increasing penetration rates, especially in Asia, an unstable camera platform, the limited mobility of straight laparoscopic instruments, the two-dimensional imaging, and a poor ergonomic position for surgeons have been regarded as limitations. Robotic technology was developed in an attempt to reduce the limitations of laparoscopic surgery. The robotic system has many advantages, including a more ergonomic position, stable camera platform and stereoscopic view, as well as elimination of tremor and subsequent improved dexterity. Current comparison data between robotic and laparoscopic rectal cancer surgery show similar intraoperative results and morbidity, postoperative recovery, and short-term oncologic outcomes. Potential benefits of a robotic system include reduction of surgeon's fatigue during surgery, improved performance and safety for intracorporeal suture, reduction of postoperative complications, sharper and more meticulous dissection, and completion of autonomic nerve preservation techniques. However, the higher cost for a robotic system still remains an obstacle to wide application, and many socioeconomic issues remain to be solved in the future. In addition, we need more concrete evidence regarding the merits for both patients and surgeons, as well as the merits compared to conventional laparoscopic techniques. Therefore, we need large-scale prospective randomized clinical trials to prove the potential benefits of robot TME for the treatment of rectal cancer