Prospective Multicenter Clinical Trial Research Articles

Effect of Drug Monitoring on Adherence and Blood Pressure: A Multicenter Randomized Clinical Trial.

Drug concentration in blood or urine is an acknowledged method to detect non-adherence. Observational studies suggest that informing patients about low or absent serum drug levels improves blood pressure (BP). We performed a multicenter randomized clinical trial to test the hypothesis that therapeutic drug monitoring (TDM) could improve drug adherence and BP in patients with uncontrolled hypertension and reduced adherence to antihypertensive drugs. Patients were ≥18 years on stable treatment with at least two antihypertensive agents. We planned to randomize 80 non-adherent patients with a systolic daytime ambulatory BP (ABPM) ≥135 mmHg to TDM-intervention or not. The control group and the study-personnel who measured BP remained uninformed about serum drug measurements throughout. All patients and physicians were blinded for BPs. Lifestyle advice and detailed information on disease process and importance of BP treatment were given to both groups. From 2017 to 2022, we randomized 46 diagnosed non-adherent from a total of 606 patients with uncontrolled hypertension. The TDM-group had a 6.7 (±14.5) mmHg reduction from 147.9 (±10.3) to 141.1 (±14.1) mmHg, and the control group experienced a 7.3 (±13.2) mmHg reduction from 147.1 (±9.2) to 139.1 (±17.4) mmHg, p=0.9 between groups. Adherence improved in both groups, 73% in the TDM group and 59% in the control group became adherent at three months, p=0.51. In our prospective multicenter clinical trial of uncontrolled and non-adherent hypertensive patients, we found no additional effect of therapeutic drug monitoring (TDM) on blood pressure and drug adherence compared with standard care.

Abstract PO4-13-04: Added Value from Patient Advocates in a Translational Working Group: the COMET Study

Abstract Introduction: A phase III multicenter prospective randomized clinical trial called “Comparing an Operation to Monitoring, with or without Endocrine Therapy (COMET)” (NCT02926911) assesses the risks/benefits of active monitoring (AM) versus surgery for women with low-risk ductal carcinoma in situ (DCIS). It is funded by the Patient-Centered Outcomes Research Institute and enrolled 997 women between 06/30/17 and 01/13/23. Research Patient Advocates (PAs) have been embedded from the study design stage and continue to provide guidance as part of the COMET leadership team. The COMET biobank is funded by independent foundations and is managed through monthly Translational Working Group (TWG) meetings. The TWG includes PAs, clinicians, pathologists, radiologists, and researchers from multiple institutions who discuss topics like categorization of biospecimens into discovery/validation sets; development of a pathology workflow/sample tracking process; use of small samples; and potential areas of future research/technologies that may improve DCIS diagnostics, prognostics, and care management. Methods: The TWG leveraged the existing Alliance Foundation Trials, LLC biobank infrastructure and facilitates the collection, submission, storage and analysis/use of blood, tissue, and breast images collected at specified timepoints and stored in central tissue/image repositories. PAs are active and integral in the TWG, assisting with logistical issues (contracts, transfer agreements, resource requests); communicating with sites; identifying study topics and biomarkers relevant to diverse patients; providing guidance on commercial predictive/prognostic tests; promoting effective stewardship of samples; ensuring overall focus remains on advancing clinical utility; and reporting translational study results to trial participants who agreed to donate samples/images. Results: Over 90% of requested samples/images have been submitted by ˃85 sites. Each patient’s biospecimens and pathology images are linked and de-identified for research. Use of artificial intelligence (AI) is being considered to assist in sample review. TWG members have complementary areas of expertise/experience and promote active stewardship for effective management of these scarce resources. PAs have played key roles concerning equitable data-sharing and acceleration of data and material transfer agreements. They have also been active in development of standards for discovery/training sets, validation test sets; communication procedures for patient cases that progress to future breast events; ways to catalog technologies (e.g., multi-omics, AI); and in research proposal review. Consensus has been achieved regarding major issues such as authorship, biospecimen custodianship, intellectual property, and criteria relevant to patient needs. Logistical barriers, including data sharing and technicalities of biospecimen release, have been resolved. The TWG also played an integral role in resolving recruitment challenges to COMET by creating standard pathology eligibility criteria, resulting in evidence-based protocol amendments that increased accrual. A retrospective review of biospecimens has been performed to determine adequacy for ensuing correlative molecular and spatial profiling studies. Conclusion: PAs help the COMET TWG set policy, and oversee biospecimen/image collection, and biobank use and sharing. PA input also facilitates equitable, transparent research studies and technology development that can improve personalized decisions for surgery versus AM in women with low-risk DCIS. PAs in the TWG aim to integrate the diagnostic and prognostic tools developed as part of the COMET study into future patient care. Citation Format: Deborah Collyar, Desiree Basila, Thomas Lynch, Stuart Schnitt, Jeffrey Marks, Siri Strand, Terry Hyslop, Sunil Badve, Mark Watson, H. T. Carisa Le-Petross, Lars Grimm, Robert West, Anna Weiss, Anna Rapperport, Lorraine King, Rachel Factor, Marc Ryser, Ann Partridge, E Shelley Hwang, Alastair Thompson. Added Value from Patient Advocates in a Translational Working Group: the COMET Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-13-04.

Metagenomic next-generation sequencing, instead of procalcitonin, could guide antibiotic usage in patients with febrile acute necrotizing pancreatitis: a multicenter, prospective cohort study.

The effectiveness of procalcitonin-based algorithms in guiding antibiotic usage for febrile acute necrotizing pancreatitis (ANP) remains controversial. Metagenomic next-generation sequencing (mNGS) has been applied to diagnose infectious diseases. The authors aimed to evaluate the effectiveness of blood mNGS in guiding antibiotic stewardship for febrile ANP. The prospective multicenter clinical trial was conducted at seven hospitals in China. Blood samples were collected during fever (T ≥38.5°C) from ANP patients. The effectiveness of blood mNGS, procalcitonin, and blood culture in diagnosing pancreatic infection was evaluated and compared. Additionally, the real-world utilization of antibiotics and the potential mNGS-guided antimicrobial strategy in febrile ANP were also analyzed. From May 2023 to October 2023, a total of 78 patients with febrile ANP were enrolled and 30 patients (38.5%) were confirmed infected pancreatic necrosis (IPN). Compared with procalcitonin and blood culture, mNGS showed a significantly higher sensitivity rate (86.7% vs. 56.7% vs. 26.7%, P <0.001). Moreover, mNGS outperformed procalcitonin (89.5 vs. 61.4%, P <0.01) and blood culture (89.5 vs. 69.0%, P <0.01) in terms of negative predictive value. Blood mNGS exhibited the highest accuracy (85.7%) in diagnosing IPN and sterile pancreatic necrosis, significantly superior to both procalcitonin (65.7%) and blood culture (61.4%). In the multivariate analysis, positive blood mNGS (OR=60.2, P <0.001) and lower fibrinogen level (OR=2.0, P <0.05) were identified as independent predictors associated with IPN, whereas procalcitonin was not associated with IPN, but with increased mortality (Odds ratio=11.7, P =0.006). Overall, the rate of correct use of antibiotics in the cohort was only 18.6% (13/70) and would be improved to 81.4% (57/70) if adjusted according to the mNGS results. Blood mNGS represents important progress in the early diagnosis of IPN, with particular importance in guiding antibiotic usage for patients with febrile ANP.

Tension band versus locking plate fixation for patella fractures - a protocol of a randomised controlled trial.

Following surgical management of patella fractures, patients commonly report pain; difficulties with weight-bearing tasks such as walking, running and climbing stairs; and restrictions in quality of life. Recently, a locking plate system for surgical management of patella fractures has been introduced. To date, no studies have compared standard treatment with tension band wiring with locking plate fixation in a randomised study design. We aim to compare the one-year patient-reported Knee Injury and Osteoarthritis Outcome subscale scores (KOOS5-subscales) after standard care tension band fixation with locking plate fixation for patients with patella fractures. This is a multicentre randomised and prospective clinical trial. A total of 122 patients will be included in the study, and the primary outcome will be the KOOS subscales at 12 months after surgery. Findings from the present study are expected to advance our understanding of outcome following surgical treatment of patella fractures. This study is funded, in part, by the Novo Nordisk Foundation, Denmark. gov ID: NCT04891549.

Application of the ankle pump method in a sitting position to evaluate calf perforating veins by color Doppler ultrasound

ObjectiveWe investigated the feasibility and efficacy of assessing calf perforating veins (PVs) using the ankle pump in a sitting position (AP-sit) method by color Doppler ultrasound. MethodsWe performed a multicenter prospective clinical trial between November 2022 and October 2023. Eligible patients with chronic venous disease and healthy controls were enrolled. The calf PVs were assessed using three different methods: manual compression in a standing position, manual compression in a sitting position, and AP-sit method. The reflux durations and detection rate of incompetent PVs (IPVs) were compared among the three methods. The number and diameter of calf PVs and distribution of IPVs were analyzed. ResultsA total of 50 patients with chronic venous disease and 50 healthy controls were included. There were 173 calves analyzed, including 97 healthy calves and 76 calves with chronic venous disease. The number of PVs per calf was higher in the diseased calves (median, 7.0; interquartile range [IQR], 6.0-8.0) than in the healthy calves (median, 5.0; IQR, 3.0-6.0; P < .001). The diameter of IPVs (median, 2.3 mm; IQR, 2.0-3.1 mm) was larger than that of competent PVs (median, 1.4 mm; IQR, 1.2-1.7 mm). Most of the IPVs (78.8%) were located in the medial and posterior middle of the calf. The reflux duration induced by the AP-sit method was greater than that induced by the manual compression methods (P < .001). Although the AP-sit method had a higher detection rate (92.0%) of IPVs than the manual compression methods (71.7% and 74.3% for standing and sitting, respectively; P < .001), especially in the distal lower leg, the manual compression methods found IPVs not found using the AP-sit method. ConclusionsDiseased calves with chronic venous disease have more PVs than do healthy calves. IPVs are commonly larger than competent PVs, with most IPVs located in the medial and posterior middle of the calf. Most importantly, the AP-sit method provides a convenient and effective approach for assessing the calf PVs, especially those located in the distal calf, as an alternative or complementary method to traditional manual compression, which is valuable in the daily practice of sonographers.

The clinical value of mNGS of bronchoalveolar lavage fluid versus traditional microbiological tests for pathogen identification and prognosis of severe pneumonia (NT-BALF):study protocol for a prospective multi-center randomized clinical trial.

Early, rapid, and accurate pathogen diagnosis can help clinicians select targeted treatment options, thus improving prognosis and reducing mortality rates of severe pneumonia. Metagenomic next-generation sequencing (mNGS) has a higher sensitivity and broader pathogen spectrum than traditional microbiological tests. However, the effects of mNGS-based antimicrobial treatment procedures on clinical outcomes and cost-effectiveness in patients with severe pneumonia have not been evaluated. This is a regional, multi-center, open, prospective, randomized controlled trial to evaluate that whether the combination of mNGS and traditional testing methods could decrease 28-day call-cause mortality with moderate cost-effectiveness. A total of 192 patients with severe pneumonia will be recruited from four large tertiary hospitals in China. Bronchoalveolar lavage fluid will be obtained in all patients and randomly assigned to the study group (mNGS combined with traditional microbiological tests) or the control group (traditional microbiological tests only) in a 1:1 ratio. Individualized antimicrobial treatment and strategy will be selected according to the analysis results. The primary outcome is 28-day all-cause mortality. The secondary outcomes are ICU and hospital length of stay (LOS), ventilator-free days and ICU-free days, consistency between mNGS and traditional microbiological tests, detective rate of mNGS and traditional microbiological tests, turn-out time, time from group allocation to start of treatment, duration of vasopressor support, types and duration of anti-infective regimens, source of drug-resistant bacteria or fungi, and ICU cost. The clinical benefits of mNGS are potentially significant, but its limitations should also be considered. ChineseClinicalTrialRegistry.org, ChiCTR2300076853. Registered on 22 October 2023.

Adjunctive Use of Bone Growth Stimulation Increases Cervical Spine Fusion Rates in Patients at Risk for Pseudarthrosis.

A prospective multicenter clinical trial (NCT03177473) was conducted with a retrospective cohort used as a control arm. The purpose of this study was to evaluate cervical spine fusion rates in subjects with risk factors for pseudarthrosis who received pulsed electromagnetic field (PEMF) treatment. Certain risk factors predispose patients to pseudarthrosis, which is associated with prolonged pain, reduced function, and decreased quality of life. Subjects in the PEMF group were treated with PEMF for 6 months postoperatively. The primary outcome measure was fusion status at the 12-month follow-up period. Fusion status was determined using anterior/posterior, lateral, and flexion/extension radiographs and computed tomography (without contrast). A total of 213 patients were evaluated (PEMF, n=160; Control, n=53). At baseline, the PEMF group had a higher percentage of subjects who used nicotine ( P =0.01), had osteoporosis ( P <0.05), multi-level disease ( P <0.0001), and were >65 years of age ( P =0.01). The PEMF group showed over two-fold higher percentage of subjects that had ≥3 risk factors (n=92/160, 57.5%) compared with the control group (n=14/53, 26.4%). At the 12-month follow-up, the PEMF group demonstrated significantly higher fusion rates compared with the control (90.0% vs. 60.4%, P <0.05). A statistically significant improvement in fusion rate was observed in PEMF subjects with multi-level surgery ( P <0.0001) and high BMI (>30kg/m 2 ; P =0.0021) when compared with the control group. No significant safety concerns were observed. Adjunctive use of PEMF stimulation provides significant improvements in cervical spine fusion rates in subjects having risk factors for pseudarthrosis. When compared with control subjects that did not use PEMF stimulation, treated subjects showed improved fusion outcomes despite being older, having more risk factors for pseudarthrosis, and undergoing more complex surgeries.

173 Electrical Stimulation Used as an Adjunct to Cervical Spine Fusion in Patients at Risk for Pseudarthrosis

INTRODUCTION: Prior studies show that pulsed electromagnetic field (PEMF) stimulation promotes bone healing and can be a valuable tool to help overcome biological deficiencies in patients at risk. The current study further evaluates the adjunct effect of PEMF in subjects undergoing cervical spinal surgery presenting with risk factors for pseudarthrosis. METHODS: A prospective multicenter clinical trial (NCT 03177473) was conducted at eleven clinical sites. Subjects undergoing cervical spinal fusion surgery with one or more risk factors for pseudarthrosis were identified for enrollment. Risk factors for pseudarthrosis included multilevel fusion, prior failed cervical spine fusion, diabetes, osteoporosis, or smoking. Subjects undergoing cervical spinal fusion were required to wear the PEMF device for 4 hours/day for 6 months post-op. Fusion status was determined at the 12-month visit using anterior/posterior, lateral, and flexion/extension radiographs and computed tomography (without contrast). NDI, EQ-5D, SF-36, and VAS for neck and arm pain were collected as secondary outcome measures. RESULTS: Out of 160 subjects, 144 (90.0%) were graded as fused (all levels) at the 12-month visit. Fusion success was 91.7% (n = 55/60), 89.0% (n = 89/100), and 90.9% (n = 20/22) for subjects with 1, 2+, or 3+ risk factors, respectively. Significant improvements in NDI, SF-36, EQ-5D, VAS-arm and VAS-neck were observed compared to baseline (p &lt; 0.001). A device compliance rate of 85.0% was observed at 3-months and 78.3% at 6-months in subjects who had successful cervical fusion. CONCLUSIONS: The PEMF bone growth stimulator device is a valuable tool to aid in fusion healing, especially in challenging populations. Subjects in this study experienced favorable fusion rates of 90% and significant improvement in patient reported outcomes despite having elevated comorbidity and/or complex surgeries.

Visual Field Outcomes in the Primary Tube Versus Trabeculectomy Study

PurposeTo describe visual field outcomes in the Primary Tube Versus Trabeculectomy (PTVT) Study. DesignCohort analysis of a prospective multicenter randomized clinical trial. SubjectsA total of 155 eyes from 155 subjects randomly assigned to treatment with tube shunt surgery (n=84) or trabeculectomy with mitomycin C (n=71). MethodsThe PTVT Study was a multicenter randomized clinical trial comparing the safety and efficacy of trabeculectomy and tube shunt surgery in eyes without prior intraocular surgery. Subjects underwent standard automated perimetry (SAP) at baseline and annually for five years. SAP tests were deemed reliable if the false positive rate was ≤15%. Tests were excluded if visual acuity was ≤20/400 or loss of ≥2 Snellen lines from baseline were attributed to a non-glaucomatous etiology. Linear mixed-effects models were used to compare rates of change in SAP mean deviation (MD) between the two treatment groups. Intraocular pressure (IOP) control was assessed by percentage of visits with IOP <18 mmHg and mean IOP. Outcome MeasuresRate of change in SAP MD during follow-up. ResultsA total of 730 SAP tests were evaluated, with an average of 4.7 tests per eye. The average SAP MD at baseline was -12.8±8.3 dB in the tube group and -12.0±8.4 dB in the trabeculectomy group (p=0.57). The mean rate of change in SAP MD was -0.32±0.39 dB/year in the trabeculectomy group and -0.47±0.43 dB/year in the tube group (p=0.23). Eyes with mean IOP 14-17.5 mmHg had significantly faster rates of SAP MD loss compared to eyes with mean IOP <14 mmHg (-0.59±0.13 vs. -0.27±0.08 dB/year, p=0.012) and eyes with only 50-75% of visits with IOP <18 mmHg had faster rates than those with 100% of visits with IOP <18 mmHg (-0.90±0.16 vs. -0.29±0.08 dB/year, p<0.001). Multivariable analysis identified older age and worse IOP control as risk factors for faster progression in both treatment groups. ConclusionsNo statistically significant difference in mean rates of visual field change was observed between trabeculectomy and tube shunt surgery in the PTVT Study. Worse IOP control was significantly associated with faster rates of SAP MD loss during follow-up. Older patients were also at risk for faster progression.

Single versus double Hem-o-lok clips to secure the apendiceal stump during laparoscopic appendectomy: a prospective randomized multicentric clinical trial

PurposePolymeric clips (Hem-o-lok ligation system) are now widely used to securing the base of the appendix during laparoscopic appendectomy. Studies comparing the use of single or double hem-o-lok clips are limited. The aim of this study was to compare the reliability of a single hem-o-lok clips with a double hem-o-lok clips for closure of an appendiceal stump.MethodsThis prospective randomized study includes patients from two centers who underwent laparoscopic appendectomy with the diagnosis of appendicitis between September 2020 and March 2023. Demographic, operative and clinical outcomes of the use of single or double hem-o-lok clips for closure of the appendiceal stump were compared. Factors affecting long postoperative hospital stay were investigated using univariate and multivariate analyzes.ResultsOne hundred forty two (48.3%) patients in the single hem-o-lok arm and 152 (51.7%) patients in the double hem-o-lok arm were included in the analysis.The shortest operative time was noted in the single hem-o-lok group (52.1 ± 19.9 versus 61.6 ± 24.9 min, p < 0.001). The median hospital stay was 1 day (range 1–10) in the single hem-o-lok group and 1 day (range 1–12) in the double hem-o-lok group, and was shorter in the single hem-o-lok arm (1.61 ± 1.56 vs 1.84 ± 1.69, p = 0.019). Based on multivariate analysis, drain placement was identified as an independent predictive factor for long hospital stay.ConclusionsThe use of single hem-o-lok clips for appendiceal stump closure during laparoscopic appendectomy is safe and effective.Trial registration NCT04387370 (http://www.clinicaltrials.gov).

Stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a non-randomised phase 2 trial

Stereotactic ablative body radiotherapy (SABR) is a novel non-invasive alternative for patients with primary renal cell cancer who do not undergo surgical resection. The FASTRACK II clinical trial investigated the efficacy of SABR for primary renal cell cancer in a phase 2 trial. This international, non-randomised, phase 2 study was conducted in seven centres in Australia and one centre in the Netherlands. Eligible patients aged 18 years or older had biopsy-confirmed diagnosis of primary renal cell cancer, with only a single lesion; were medically inoperable, were at high risk of complications from surgery, or declined surgery; and had an Eastern Cooperative Oncology Group performance status of 0-2. A multidisciplinary decision that active treatment was warranted was required. Key exclusion criteria were a pre-treatment estimated glomerular filtration rate of less than 30 mL/min per 1·73 m2, previous systemic therapies for renal cell cancer, previous high-dose radiotherapy to an overlapping region, tumours larger than 10 cm, and direct contact of the renal cell cancer with the bowel. Patients received either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions for tumours more than 4 cm to 10 cm in maximum diameter. The primary endpoint was local control, defined as no progression of the primary renal cell cancer, as evaluated by the investigator per Response Evaluation Criteria in Solid Tumours (version 1.1). Assuming a 1-year local control of 90%, the null hypothesis of 80% or less was considered not to be worthy of proceeding to a future randomised controlled trial. All patients who commenced trial treatment were included in the primary outcome analysis. This trial is registered with ClinicalTrials.gov, NCT02613819, and has completed accrual. Between July 28, 2016, and Feb 27, 2020, 70 patients were enrolled and initiated treatment. Median age was 77 years (IQR 70-82). Before enrolment, 49 (70%) of 70 patients had documented serial growth on initial surveillance imaging. 49 (70%) of 70 patients were male and 21 (30%) were female. Median tumour size was 4·6 cm (IQR 3·7-5·5). All patients enrolled had T1-T2a and N0-N1 disease. 23 patients received single-fraction SABR of 26 Gy and 47 received 42 Gy in three fractions. Median follow-up was 43 months (IQR 38-60). Local control at 12 months from treatment commencement was 100% (p<0·0001). Seven (10%) patients had grade 3 treatment-related adverse events, with no grade 4 adverse events observed. Grade 3 treatment-related adverse events were nausea and vomiting (three [4%] patients), abdominal, flank, or tumour pain (four [6%]), colonic obstruction (two [3%]), and diarrhoea (one [1%]). No treatment-related or cancer-related deaths occurred. To our knowledge, this is the first multicentre prospective clinical trial of non-surgical definitive therapy in patients with primary renal cell cancer. In a cohort with predominantly T1b or larger disease, SABR was an effective treatment strategy with no observed local failures or cancer-related deaths. We observed an acceptable side-effect profile and renal function after SABR. These outcomes support the design of a future randomised trial of SABR versus surgery for primary renal cell cancer. Cancer Australia Priority-driven Collaborative Cancer Research Scheme.

Surgical Treatment of Scaphoid Fractures: Recommendations for Management.

Background: Several operative treatments exist for scaphoid fractures, varying by approach (e.g., ercutaneous, volar, or dorsal), implant type (e.g., screw or Kirschner wire), and bone raft choice (e.g., none, nonvascularized, or vascularized). Many previous systematic eviews and meta-analyses have investigated outcomes following different surgicalÚpproaches, the use of vascularized versus nonvascularized bone graft for scaphoidßracture nonunions, and treatment for specific fracture patterns. However, given the advancements n scaphoid fracture treatment in recent years, there is a need for updated treatment recommendations hat would be beneficial to hand surgeons. Purpose: We present a comprehensive review of the operative treatment of scaphoid fractures based on recent literature and propose a unified treatment algorithm for managing these fractures. Methods: The English-language literature was searched from 2002 to 2023 for high evidence level (e.g., randomized trials), review, and meta-analysis articles with the following search terms: "scaphoid, "u8220"scaphoid" AND "nonunion, " and "scaphoid" AND "malunion. " Each article was creened by the authors to determine the scaphoid fracture scenario addressed and ubsequent treatment recommendations. The findings from article reviews were then rganized by scaphoid fracture types in this manuscript. Results: A total of 95 pertinent articles were ultimately selected and used as the basis for reviewing different scaphoid fracture scenarios. A treatment algorithm was then proposed based on literature review. Conclusion: This summary of the recent literature can guide hand surgeons in addressing scaphoidßractures. Future research in scaphoid fracture treatment, particularly for nonunions, would be most beneficial n the form of systematic review, meta-analysis, or multicenter prospective randomized clinical trials. Level of Evidence: IV.

Patient values in patient-provider communication about participation in early phase clinical cancer trials: a qualitative analysis before and after implementation of an online value clarification tool intervention

BackgroundPatients with advanced cancer who no longer have standard treatment options available may decide to participate in early phase clinical trials (i.e. experimental treatments with uncertain outcomes). Shared decision-making (SDM) models help to understand considerations that influence patients’ decision. Discussion of patient values is essential to SDM, but such communication is often limited in this context and may require new interventions. The OnVaCT intervention, consisting of a preparatory online value clarification tool (OnVaCT) for patients and communication training for oncologists, was previously developed to support SDM. This study aimed to qualitatively explore associations between patient values that are discussed between patients and oncologists during consultations about potential participation in early phase clinical trials before and after implementation of the OnVaCT intervention.MethodsThis study is part of a prospective multicentre nonrandomized controlled clinical trial and had a between-subjects design: pre-intervention patients received usual care, while post-intervention patients additionally received the OnVaCT. Oncologists participated in the communication training between study phases. Patients’ initial consultation on potential early phase clinical trial participation was recorded and transcribed verbatim. Applying a directed approach, two independent coders analysed the transcripts using an initial codebook based on previous studies. Steps of continuous evaluation and revision were repeated until data saturation was reached.ResultsData saturation was reached after 32 patient-oncologist consultations (i.e. 17 pre-intervention and 15 post-intervention). The analysis revealed the values: hope, perseverance, quality or quantity of life, risk tolerance, trust in the healthcare system/professionals, autonomy, social adherence, altruism, corporeality, acceptance of one’s fate, and humanity. Patients in the pre-intervention phase tended to express values briefly and spontaneously. Oncologists acknowledged the importance of patients’ values, but generally only gave ‘contrasting’ examples of why some accept and others refuse to participate in trials. In the post-intervention phase, many oncologists referred to the OnVaCT and/or asked follow-up questions, while patients used longer phrases that combined multiple values, sometimes clearly indicating their weighing.ConclusionsWhile all values were recognized in both study phases, our results have highlighted the different communication patterns around patient values in SDM for potential early phase clinical trial participation before and after implementation of the OnVaCT intervention. This study therefore provides a first (qualitative) indication that the OnVaCT intervention may support patients and oncologists in discussing their values.Trial registrationNetherlands Trial Registry: NL7335, registered on July 17, 2018.

Magnetic resonance-guided focused ultrasound for essential tremor: a prospective, single center, single-arm study.

JOURNAL/nrgr/04.03/01300535-202409000-00041/figure1/v/2024-01-16T170235Z/r/image-tiff The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor. In 2018, the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital. This prospective, single center, open-label, single-arm study was part of a worldwide prospective multicenter clinical trial (ClinicalTrials.gov Identifier: NCT03253991) conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population. From 2019 to 2020, 10 patients with medication refractory essential tremor were recruited into this open-label, single arm study. The treatment efficacy was determined using the Clinical Rating Scale for Tremor. Safety was evaluated according to the incidence and severity of adverse events. All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus. At the baseline assessment, the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3 ± 3.6, and this improved after treatment to 23.1 ± 6.4 at a 12-month follow-up assessment. A total of 50 adverse events were recorded, and 2 were defined as serious. The most common intraoperative adverse events were nausea and headache. The most frequent postoperative adverse events were paresthesia and equilibrium disorder. Most of the adverse events were mild and usually disappeared within a few days. Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective, with a good safety profile, for patients in Chinese mainland.

The performance of a deep learning system in assisting junior ophthalmologists in diagnosing 13 major fundus diseases: a prospective multi-center clinical trial

Artificial intelligence (AI)-based diagnostic systems have been reported to improve fundus disease screening in previous studies. This multicenter prospective self-controlled clinical trial aims to evaluate the diagnostic performance of a deep learning system (DLS) in assisting junior ophthalmologists in detecting 13 major fundus diseases. A total of 1493 fundus images from 748 patients were prospectively collected from five tertiary hospitals in China. Nine junior ophthalmologists were trained and annotated the images with or without the suggestions proposed by the DLS. The diagnostic performance was evaluated among three groups: DLS-assisted junior ophthalmologist group (test group), junior ophthalmologist group (control group) and DLS group. The diagnostic consistency was 84.9% (95%CI, 83.0% ~ 86.9%), 72.9% (95%CI, 70.3% ~ 75.6%) and 85.5% (95%CI, 83.5% ~ 87.4%) in the test group, control group and DLS group, respectively. With the help of the proposed DLS, the diagnostic consistency of junior ophthalmologists improved by approximately 12% (95% CI, 9.1% ~ 14.9%) with statistical significance (P < 0.001). For the detection of 13 diseases, the test group achieved significant higher sensitivities (72.2% ~ 100.0%) and comparable specificities (90.8% ~ 98.7%) comparing with the control group (sensitivities, 50% ~ 100%; specificities 96.7 ~ 99.8%). The DLS group presented similar performance to the test group in the detection of any fundus abnormality (sensitivity, 95.7%; specificity, 87.2%) and each of the 13 diseases (sensitivity, 83.3% ~ 100.0%; specificity, 89.0 ~ 98.0%). The proposed DLS provided a novel approach for the automatic detection of 13 major fundus diseases with high diagnostic consistency and assisted to improve the performance of junior ophthalmologists, resulting especially in reducing the risk of missed diagnoses. ClinicalTrials.gov NCT04723160

The Management of Children with Pre-School Medulloblastoma – A Review of Four Decades of Multi-Disciplinary and Multi-Institutional Collaboration.

Background: The management and consequent survival and quality of survival for young children with medulloblastoma have undergone substantial improvement over the last four decades. While many of these changes reflect improvements in pediatric neurosurgical, neuro- imaging and radiation oncologic technology and training, as well as in supportive care experience and expertise, this review will focus particularly upon improvements in chemotherapeutic approaches. Methods: This review focuses only upon prospective clinical trials conducted in young children with newly-diagnosed medulloblastoma since the 1980s. The upper age limits for these trials varied from under three to up to six years of age at diagnosis. Results: Certain but not all trials endeavoring to improve outcomes for young children with now- recognized pathological and molecular low-risk characteristics, specifically the Sonic Hedgehog (SHH) sub-type, representing some 50-60% of young children with medulloblastoma, have reaped substantial gains in event-free and overall survival, irradiation-free survival as well as neuropsychological outcomes. Those successful trials utilized either induction including intravenous high-dose methotrexate and intraventricular (intra-Ommaya) methotrexate without consolidation by marrow-ablative chemotherapy with autologous hematopoietic progenitor cell rescue (AuHPCR), or induction with or without intravenous high-dose methotrexate (but not intra-ventricular methotrexate) followed by consolidation with marrow-ablative chemotherapy with AuHPCR. These two approaches have consistently produced superior outcomes compared with other trials. For children with molecularly-characterized Groups 3 or 4 medulloblastoma, representing those at high-risk of relapse, some modest improvements have been made over the years, but much room for improvement remains, especially for those presenting with the highest- risk molecular characteristics (CMYC-amplified Group 3 medulloblastoma) as well as for children with metastatic disease at initial diagnosis. Conclusions: Substantial gains in improving outcomes for young children with medulloblastoma have been achieved with acceptable short- and long-term morbidities of treatment. However, the inclusion of intra-ventricular therapies (conventional chemotherapeutic, radio-labeled monoclonal antibody or adaptive cellular immunotherapeutic approaches) as well as the identification of targeted systemic therapies (biological and/or immunological) and their incorporation into prospective multi-center clinical trials, must be investigated prospectively if we are to improve outcomes for those children at high-risk for relapse, even with the inclusion of refined irradiation therapeutic approaches.

Robotic-Assisted Proctosigmoidectomy vs. Laparoscopic-Assisted Soave Pull-Through for Hirschsprung’s Disease: Medium-Term Outcomes From a Prospective Multicenter Study

Objective: To compare the surgical outcomes of robotic-assisted proctosigmoidectomy (RAP) and laparoscopic-assisted Soave pull-through (LAP) for children with Hirschsprung’s disease (HD). Summary Background Data: LAP and RAP have been developed for minimally invasive pull-through of HD, but the clinical benefits of robotic-assisted versus laparoscopic-assisted approaches have yet to be proven in a multicenter prospective study. Methods: This study was a prospective multicenter clinical trial conducted on children with rectosigmoid/descending HD from July 2015 to June 2022, with registration in the Chinese Clinical Trial Registry (ChiCTR2000035220). The primary outcome was the medium-term functional outcomes in children aged ≥4 years based on bowel functional scores, which were assessed and compared between LAP and RAP. Results: A total of 328 consecutive patients (RAP=165, LAP=163) were approached who were considered eligible for elective minimally invasive endorectal pull-through, and 219 patients aged ≥4 years of age completed follow-up (RAP=109, LAP=110). The transanal dissection length and anal traction time were significantly shorter in RAP than those in LAP (0.30 cm vs. 3.70 cm, P &lt;0.001; 45 min vs. 62 min, P &lt;0.001). The RAP group had significantly lower urinary retention rate (0% vs. 5.52%, P=0.006), while other short-term results between two groups were not significantly different. The medium-term overall BFS scores were comparable between two groups; however, among the subgroup of children aged ≤ 3 months at surgery, the RAP group had better anal canal resting pressure at one year postoperatively and amounted to better annual POFC scores at 4-7 years old postoperatively (all P &lt;0.05). Conclusions: RAP and LAP should have similar medium-term bowel functional outcomes in HD children, but RAP may be associated with a slight functional benefit in infants operated on below age 3 months, requiring further investigation in larger case cohorts.

Metronomic Temozolomide (mTMZ) and Bevacizumab—The Safe and Effective Frontier for Treating Metastatic Neuroendocrine Tumors (NETs): A Single-Center Experience

Addressing the persistent challenges in treating metastatic neuroendocrine tumors (NETs) demands ongoing refinement and innovation in therapeutic strategies. This study investigates the potential advantages of combining metronomic temozolomide (mTMZ) with bevacizumab for patients diagnosed with metastatic NETs, particularly focusing on those with a Ki-67 index under 55%. Data from 30 patients were analyzed, using key performance indicators such as progression-free survival (PFS), overall survival (OS), and response rates to therapy, to gauge the treatment’s efficacy. The results were encouraging: the median PFS recorded was 16.3 months, and the OS was 25.9 months. The disease control rate (DCR) reached an impressive 86.7%, and the objective response rate (ORR) stood at 63.3%. The treatment regimen was well-tolerated, with no reported instances of grade 4 toxicities. Such a safety profile indicates that this regimen may be particularly advantageous for older, fragile patients who might struggle with conventional dosage levels. These initial findings suggest that the mTMZ and bevacizumab combination could potentially rival the conventional temozolomide–capecitabine therapy in managing metastatic NETs. We aimed to meticulously assess the efficacy of the mTMZ and bevacizumab combination in treating metastatic NETs. Given the initial promising results, a more conclusive understanding of its efficacy will require further research through larger, multicenter prospective clinical trials.

Effect of different application duration of a venous foot pump on prevention of venous thromboembolism after hip and knee arthroplasty: a multicenter prospective clinical trial

ObjectiveTo investigate the optimal duration of applying a venous foot pump (VFP) in the prevention of venous thromboembolism (VTE) following hip and knee arthroplasty.MethodsA total of 230 patients undergoing hip and knee arthroplasty between March 2021 and March 2022 in orthopaedic departments of four major teaching hospitals were prospectively enrolled. Patients were randomly divided into five groups based on the duration of the VFP application. Postoperative deep vein thromboses (DVT), including proximal, distal, and intermuscular DVT, were recorded for analysis. Postoperative blood coagulation examinations, such as D-dimer and active partial thromboplastin time (APTT), pain outcome, and degree of comfort were also collected.ResultsTwo of the 230 patients withdrew due to early discharge from the hospital, and 228 patients were included in the final analysis. The mean age was 60.38 ± 13.33 years. The baseline characteristics were comparable among the five groups. Compared with the other groups, patients treated with 6-hour VFP had the lowest incidence of DVT (8.7%, 4/46), followed by those treated with 1-hour VFP (15.2%, 7/46), 12-hour VFP (15.6%, 7/45), 18-hour VFP(17.8%, 8/45) and 20-hour VFP(21.7%, 10/46), but with no significant difference (P = 0.539). Regarding postoperative blood coagulation examinations, patients treated with 6-hour VFP had the lowest D-dimer (P = 0.658) and the highest APTT (P = 0.262) compared with the other four groups. 6-hour VFP also had the lowest pain score (P = 0.206) and the highest comfort score (P = 0.288) compared with the other four groups.ConclusionsSix hours may be the optimal duration of applying VFP for the prevention of VTE in patients undergoing hip and knee arthroplasty in terms of VTE incidence, postoperative blood coagulation examinations, pain outcomes, and comfort scores.

To radiate or not to radiate: that is the question?-a commentary on "Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial".

To radiate or not to radiate: that is the question?-a commentary on "Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial".