Nonrandomized Clinical Trial Research Articles

Development of the continuous ambulatory vestibular assessment (CAVA) system to provide an automatic diagnosis for vestibular conditions: protocol for a multicentre, single-arm, non-randomised clinical trial

IntroductionDizziness is a common symptom that can occur in an unpredictable and episodic manner leading to the imprecise reporting of symptoms. Patients will often see many specialists before receiving a...

Updated survival outcome of regorafenib, ipilimumab, and nivolumab in refractory microsatellite stable non-liver metastatic colorectal cancer: A phase I nonrandomized clinical trial

BackgroundCombination regorafenib, ipilimumab, and nivolumab (RIN) was evaluated in a phase 1 nonrandomized study (NCT04362839) of refractory microsatellite stable (MSS) metastatic colorectal cancer. Promising antitumor activity was previously reported in the non-liver metastatic (NLM) population. This updated analysis describes long-term survival outcomes in the NLM cohort and highlights durable remissions with potential cure following completion of RIN therapy. MethodsBetween May 2020 and January 2022, 39 patients with refractory MSS metastatic colorectal cancer were enrolled. Patients received RIN until progression, unacceptable toxicity, or completion at two years. The primary endpoint was recommended phase 2 dose (RP2D) selection. Secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) at the RP2D level. Results22 patients with refractory non-liver metastatic MSS colorectal cancer were treated at the RP2D of RIN. ORR was 36.4 % (8/22 patients), and median PFS was 5.0 months (95 % CI: 3–9). After a median follow-up of 42 months, the 1-, 2-, and 3-year PFS rates were 24.1 %, 24.1 %, and 19.3 % by RECIST. The median OS was 27.5 months (95 % CI: 14.0 to NE). At data cutoff, 6 patients had ongoing clinical benefit, including 3 responders who remain disease-free > 18 months after treatment completion. ConclusionWith extended follow-up, RIN combination therapy demonstrated durable clinical benefit in a subset of patients with NLM MSS metastatic colorectal cancer, including potential cure in 3 responders who remain disease-free > 18 months after treatment completion.

The Influence of Health Education on Vaccination Coverage and Knowledge of the School Population Related to Vaccination and Infection Caused by the Human Papillomavirus

Background/Objectives: Human papillomavirus (HPV) is a causative agent of infections and cancers of the reproductive and digestive tract, and vaccination is the most effective prevention method. This research aimed to assess the impact of health education on vaccination coverage and knowledge of the school population related to HPV infection and vaccination. Methods: This non-randomized clinical trial included 170 participants out of the 221 students in the generation of 2022/2023, who were divided into a group of Subjects and Controls and who self-assessed their knowledge and tested knowledge at four and two time points, respectively. Results: The study examined whether there is a difference in the share of vaccinated students of the entire generation compared to the previous generation (62% vs. 47%). The self-assessment and assessment of one’s knowledge in the group of subjects was significantly lower before education than during other time points during the research. At “moment zero”, there was no significant difference in the knowledge assessment between the groups. However, after 8 weeks, the knowledge assessment was significantly higher in the Subject group. Conclusions: The results suggest a positive impact of health education, which may contribute to raising awareness about the importance of prevention and vaccination against HPV.

Rosuvastatin effect on atherosclerotic plaque microcalcification

Abstract Background and Aims Atherosclerotic plaque fluorine-18 sodium fluoride (18F-NaF) uptake on positron emission tomography with computed tomography (PET-CT) identifies active microcalcification and has been shown to correlate with clinical instability in patients with cardiovascular (CV) disease. Statin therapy promotes coronary macrocalcification over time. Our aim was to investigate rosuvastatin effect on atheroma 18F-NaF uptake. Methods Subjects with high CV risk but without CV events underwent 18F-NaF-PET-CT in a single-centre. Those with subclinical atherosclerosis and significant 18F-NaF plaque uptake were included in a single-arm clinical trial, treated with rosuvastatin 20mg/daily for six months, and re-evaluated by 18F-NaF-PET-CT. Primary endpoint was reduction in maximum atheroma 18F-NaF uptake in the coronary, aortic or carotid arteries, assessed by the tissue-to-background ratio (TBR). The secondary endpoint was corrected uptake per lesion (CUL) variation. Results Forty individuals were enrolled and 38 included in the pharmacological trial; mean age was 64 years-old, two-thirds were male and most were diabetic. The 10-year expected CV risk was 9.5% (6.0-15.3) for SCORE2 and 31.7±18.7% for ASCVD systems. After six months of rosuvastatin treatment (n=34), low-density lipoprotein cholesterol lowered from 133.6±33.8 to 58.8±20.7 mg.dL-1 (60% relative reduction, p<0.01). There was a significant 19% reduction in maximum plaque 18F-NaF uptake after treatment, from 1.96 (1.78-2.22) to 1.53 (1.40-2.10), p<0.001 (primary endpoint analysis). The secondary endpoint CUL was reduced by 23% (p=0.003). Conclusion In a single-centre non-randomized clinical trial of high CV risk individuals with subclinical atherosclerosis, the maximum atherosclerotic plaque 18F-NaF uptake was significantly reduced after six months of high-intensity statin.Graphical abstractTrial design

Outcome of posterior decompression by L1 laminectomy, transpedicular fixation, posterolateral fusion in burst fracture L1 with incomplete spinal cord injury

Introduction: Burst fractures are more severe than compression fractures as the bones spread out in all directions and may damage the spinal cord, leading to paralysis or nerve injury. This study aims to find the surgical outcomes of Posterior Decompression by L1 Laminectomy in terms of burst fracture with incomplete spinal cord injury. Methods: 48 adult patients with burst fractures with incomplete spinal injury came to NITR from June 2023 to May 2024. In this non-randomized clinical trial, the outcomes of decompression by L1 laminectomy were analysed by using the canal encroachment ratio, while deformity correction was assessed using the sagittal Cobb angle and the percentage of anterior vertebral height for the treatment of L1 burst fracture with incomplete spinal cord injury. Results: The patients were followed up for an average of 12 months. The mean operation time was 154.53 minutes, mean intraoperative blood loss of 48.84 mL, and the mean incision length was 7.78 cm. The canal encroachment ratio decreased significantly, as well as the sagittal Cobb angle, and anterior vertebral percentage height increased. Oswestry Disability Index, and American Spinal Injury Association impairment scale classification were significant. Conclusions: Posterior decompression combined with Transpedicular Fixation and Posterolateral Fusion in the treatment of Burst Fracture L1 with Incomplete Spinal Cord Injury is safe and effective.

Dual Immune Checkpoint Inhibition in Patients With Aggressive Thyroid Carcinoma

Aggressive thyroid carcinoma, including radioiodine refractory (RAIR) differentiated thyroid carcinoma (DTC), medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC), are associated with significant morbidity and mortality and have limited therapeutic options. Distinct immune profiles have been identified in thyroid cancer subtypes suggesting they may be susceptible to immune checkpoint inhibition. To evaluate the efficacy of anti-programmed cell death 1 nivolumab and anti-cytotoxic lymphocyte-associated protein 4 ipilimumab in patients with aggressive thyroid carcinoma. This phase 2 nonrandomized clinical trial enrolled patients with RAIR DTC in a single center from October 2017 to May 2019, with exploratory cohorts in MTC and ATC. The data were analyzed between June 2021 and September 2023. Intravenous nivolumab, 3 mg/kg, every 2 weeks and ipilimumab, 1 mg/kg, every 6 weeks until disease progression, intolerable adverse events, or a maximum duration of 2 years. The primary end point of the study was objective response rate (ORR) in RAIR DTC, which was scored according to RECIST (Response Evaluation Criteria in Solid Tumours), version 1.1. Key secondary end points included safety, progression-free survival, overall survival, and biomarker analyses. A total of 51 patients were registered, and 49 patients were evaluable for analysis. The median (range) age was 65 years (30-88 years), and 25 participants (51%) were female. ORR in the DTC cohort was 9.4% (3/32 [95% CI, 2.8%-28.5%]), with all partial responses in either oncocytic carcinoma (2/6 [33.0%]) or poorly differentiated thyroid carcinoma (1/5 [20.0%]). Clinical benefit rates were 62.5% (20/32) in the overall DTC cohort, including 83.3% (5/6) in oncocytic carcinoma and 40% (2/5) in poorly differentiated thyroid carcinoma. ORR in the exploratory ATC cohort was 30.0% (3/10 [95% CI, 6.7%-65.2%]), with a clinical benefit rates of 50.0% (5/10). No responses were observed in the exploratory MTC cohort. The safety profile was similar to prior reports with dual immune checkpoint inhibition (pruritus, rash, diarrhea, fatigue, and elevation of lipase and liver enzymes). The presence of NRAS tumor genetic sequence variations, but not BRAF V600E, was associated with worse outcomes. This phase 2 nonrandomized clinical trial reported clinical activity of dual immune checkpoint inhibition in aggressive thyroid cancer. The study did not meet its end point in the primary population of RAIR DTC and does not support further investigation in non-biomarker-selected DTC. However, the signal observed in ATC may merit further evaluation. ClinicalTrials.gov Identifier: NCT03246958.

Anti–Programmed Death Ligand 1 Plus Targeted Therapy in Anaplastic Thyroid Carcinoma

Anaplastic thyroid carcinoma (ATC) is a rare and lethal cancer. Although progress has been made in recent years in patients with mutated BRAF tumors, those who respond initially eventually die of their disease; furthermore, there are no approved therapies for non-BRAF mutated tumors. To determine whether treatment with matched-targeted therapy plus immune checkpoint inhibitors were associated with improved overall survival (OS). A phase 2 trial at a single center, tertiary institution with parallel cohorts, assigning treatment with targeted therapy according to the tumor mutation status. Patients with mutated BRAF V600E tumors received vemurafenib/cobimetinib plus atezolizumab (cohort 1); those with mutated RAS (NRAS, KRAS, or HRAS) or NF1/2 tumors received cobimetinib plus atezolizumab (cohort 2). Patients without any of these variants were assigned to receive bevacizumab plus atezolizumab (cohort 3). Patients were enrolled from August 3, 2017, to July 7, 2021. All consecutive, systemic therapy-naive patients with ATC with active disease and who met eligibility criteria were considered for participation. The analysis was conducted in September 2023. Patients were assigned to targeted therapy based on the driver mutation as follow: BRAF V600E (cohort 1, vemurafenib plus cobimetinib), RAS/NF (cohort 2, cobimetinib), or non-BRAF/RAS/NF (cohort 3, bevacizumab). All received atezolizumab. The primary outcome of the study was median OS of the entire targeted therapy cohort, compared with historical median OS of 5 months. Forty-three patients with ATC were enrolled in the targeted therapy cohorts, of which 42 were included in the primary analysis. The median OS in patients across these 3 cohorts was 19 months (95% CI, 7.79-43.24). Median OS and progression-free survival per cohort were as follows: cohort 1: 43 months (95% CI, 16-not estimable [NE]), 13.9 months (6.6-64.1); cohort 2: 8.7 months (95% CI, 5.1-37.0) and 4.8 months (1.8-14.7); cohort 3 (vascular endothelial growth factor inhibitor group): 6.21 months (4.1-NE) and 1.3 months (1.3-NE), respectively. In this nonrandomized clinical trial, atezolizumab combined with targeted therapy resulted in a longer median OS than historical landmark, achieving the study's primary end point, with cohort 1 achieving the longest OS. ClinicalTrials.gov Identifier: NCT03181100.

LUDT-ADHF trial: Lung ultrasound-guided diuretic therapy for hospitalized patients with acute decompensated heart failure: An open-label clinical trial

Background Acute Decompensated Heart Failure (ADHF) constitutes a major reason for hospital admissions and significantly contributes to increased morbidity and mortality. Limited research indicates that lung ultrasound (LUS) may enhance the care for patients with ADHF.Objectives The purpose of this study was to evaluate the impact of LUS-guided diuretic therapy on reducing length of hospital stay (LOS) and 90-day readmissions among patients with ADHF.Methods This open-label, non-randomized clinical trial included patients with ADHF managed with diuretics based on LUS findings of B-lines and pleural effusion (LUS group) compared to those receiving standard care (control group). The primary outcome was LOS during the index admission, and secondary outcomes included 90-day ADHF readmissions, all-cause readmissions, and safety parameters like acute kidney injury, hypokalemia, and hypotension.Results The study included a total of 77 patients, segregated into two groups: control and LUS. The median age of the patients was 68 years, with women slightly outnumbering men (53.25%, n=41). The most prevalent comorbidities were hypertension (88.31%, n=68), diabetes mellitus (59.74%, n=46), and chronic kidney disease (66.23%, n=51). The LUS group had a shorter LOS, though not statistically significant (4 vs five days, p= 0.175). Patients in the LUS group had significantly fewer 90-day ADHF readmissions compared to the control group (10.53% vs. 35.9%; p<0.01). Survival analysis demonstrated that the LUS group had a longer time to 90-day ADHF readmissions, with a hazard ratio (HR) of 0.24 (95% CI: 0.08–0.75, p=0.014). For 90-day all-cause readmissions, the LUS group also showed a longer time to readmission compared to controls, with an HR of 0.45 (95% CI: 0.200–1.005, p=0.046). For other safety measures, there was no significant difference in the incidence of adverse events, including acute kidney injury, hypokalaemia, or hypotension, between the LUS and control groups.Conclusion LUS might reduce in-hospital mortality and readmissions among adults with acute decompensated HF. However, further double-blinded randomized clinical trials are needed to confirm these preliminary results.

Impact of Multi-Professional Intervention on Health-Related Physical Fitness and Biomarkers in Overweight COVID-19 Survivors for 8 and 16 Weeks: A Non-Randomized Clinical Trial.

Considering the diverse symptomatology of COVID-19-ranging from mild to severe cases-multi-professional interventions are crucial for enhancing physical recovery, nutritional status, and mental health outcomes in affected patients. Thus, this study aimed to investigate the effects of such an intervention on health-related physical fitness and biomarkers in overweight COVID-19 survivors with varying degrees of symptom severity after 8 weeks and 16 weeks. This non-randomized clinical trial included 59 overweight COVID-19 survivors (32 males and 27 females) divided into three groups: mild (n = 31), moderate (n = 13), and severe/critical (n = 15). The participants underwent a multi-professional program and were assessed for anthropometric and body composition (primary outcome), as well as physical fitness and biochemical markers (secondary outcome) 8 and 16 weeks before the intervention. After 8 weeks, time effects were observed for the maximum isometric handgrip strength (p < 0.001), maximum isometric lumbar-traction strength (p = 0.01), flexibility (p < 0.001), abdominal strength-endurance (p < 0.001), the sit-and-stand test (p < 0.001), maximum oxygen consumption (p < 0.001), and distance covered in the 6 min walk test (p < 0.001). Additionally, time effects were also observed for fat mass (p = 0.03), body fat percentage (p = 0.02), abdominal circumference (p = 0.01), total cholesterol (p < 0.001), low-density lipoproteins (p < 0.001), and glycated hemoglobin (p < 0.001), with lower values after multi-professional interventions. After 16 weeks, the systolic and diastolic blood pressure showed significant reductions independently of the intervention group (p < 0.001). These findings suggest that multi-professional interventions can provide substantial benefits for post-COVID-19 patients, regardless of the severity of their initial symptoms.

Allogenic MSC infusion in kidney transplantation recipients promotes within 4 hours distinct B cell and T cell phenotypes.

Infusion of mesenchymal stromal cells (MSCs) has been proposed as immune-modulatory therapy in solid organ transplantation. The use of allogenic MSCs could improve standardization and allow for direct availability of the product. The nonrandomized phase Ib Neptune clinical trial provided safety and feasibility data on the use of allogenic bone-marrow-derived MSCs, infused in 10 patients at week 25 and 26 post kidney transplantation. Here, we performed detailed analysis on the peripheral blood immune cell composition of these patients up to 52 weeks post transplantation. We used a 40 marker antibody panel with mass cytometry to assess potential effects of MSC therapy on the immune system. We showed minor changes in major immune lineages at week 27, 34 and 52 post kidney transplantation after MSC infusion at week 25 and week 26, confirming previous data with regular flow cytometry. However, in a direct comparison between pre- and post MSC infusion, as soon as 4 hours after MSC infusion, we observed a significant increase in cell numbers of B cell and T cell subsets that shared a unique expression of CD11b, CD11c, CD38, CD39, and Ki-67. Exploring these CD11b+CD11c+CD38+CD39+Ki-67+ B cells and T cells in the context of MSC infusion after kidney transplantation may be a promising avenue to better understand the immunological effects of MSC therapy.

The Impact of Type 2 Diabetes Mellitus on Non-Surgical Periodontal Treatment: A Non-Randomized Clinical Trial.

Background/Objectives: Periodontitis (P), a chronic inflammatory condition that affects the supportive tissues around the teeth, is three to four times more prevalent in individuals with diabetes mellitus (DM), with a direct correlation between its severity and the levels of glycosylated hemoglobin (HbA1c). This study aimed to evaluate the periodontal clinical parameters following non-surgical periodontal treatment (NSPT) in P patients with or without type 2 DM. Methods: Forty patients with P were divided into two groups: Group DM/P and Group P. All the patients were assessed at baseline and at 90 and 180 days after receiving NSPT. The parameters evaluated included the HbA1c level, plaque index (PI), probing pocket depth (PPD), clinical attachment level (CAL), and bleeding on probing (BoP). A statistical analysis was performed with a significance level set at α = 5%. Results: There were significant differences in the HbA1c levels between the DM/P and P groups at baseline, 90, and 180 days, as expected. Importantly, the HbA1c levels did not change after NSPT. Group P showed a significant reduction in both the PI and the BoP values at 90 and 180 days (p < 0.05). In contrast, Group DM/P demonstrated a significant increase in the percentage of sites with a PPD ≥ 5 mm at 180 days (p < 0.05). Additionally, Group P exhibited an increase in sites with a PPD ≤ 4 mm and a decrease in sites with a PPD ≥ 5 mm at both 90 and 180 days (p < 0.05). Conclusions: Our findings suggest that DM may compromise the effectiveness of NSPT, potentially hindering favorable outcomes during the follow-up period.

Cone beam computed tomography changes upon oral appliance therapy for adult patients with obstructive sleep apnea: A non-randomized clinical trial.

Obstructive sleep apnea (OSA) is caused by narrowing or obstruction of the airway lumen at single or multiple levels of the airway, starting from the nasal cavity up to the larynx. Oral appliance therapy for the management of OSA is prescribed as an alternative treatment option for patients with mild to moderate OSA who fail to adhere to Continuous Positive Airway Pressure (CPAP) therapy. Treatment with oral appliances addresses the craniofacial deficiencies that cause OSA by providing means to mandibular advancement and palatal expansion, thus opening the airways and potentially preventing airway collapse during sleep. Imaging the upper airway is employed to investigate the narrowing or the obstruction in the airway. Three-dimensional imaging modalities such as cone beam computed tomography (CBCT) allow for detecting obstructions before commencing treatment and for evaluating changes in the upper airway dimensions after treatment. To evaluate the effect of the biomimetic oral appliance therapy (BOAT) device on the airway measurements taken from a CBCT before and after treatment in correlation with the changes in the AHI. A non-randomized clinical trial. About 17 patients with mild-moderate OSA (9 males, 8 females; age, mean [SD]: 45.76 [10.31]) underwent BOAT therapy. Subjects had 2 months of follow-up visits, including examinations for progress and adjustment of the appliances. The mean apnea-hypopnea index (AHI) with no appliance in the mouth before BOAT and after treatment was recorded. The midpalate screw mechanism of the appliance was advanced once per week. The subjects were asked to wear the appliance for 10 to 12 h/d and night. Pre and Post CBCT were taken. Paired T-test was used to analyze the results. The treatment duration was 15.4 ± 6.3 months. Before treatment, at the diagnosis stage, the mean AHI of the sample (n = 17) was 24.0. After treatment, the mean AHI fell by 5% to 22.8% (P = .019), indicating enhanced upper airway functions. Airway measurements from the CBCT were not statistically significant despite improvement in the polysomnographic parameters. CBCT is a valuable tool for airway assessment and the determination of upper airway anatomic risk factors for OSA.

Effects of cognitive training and group psychotherapy on cognitive performance of post COVID-19 patients: an exploratory and non-randomized clinical trial.

Cognitive complaints are common signs of the Post COVID-19 (PC) condition, but the extent and type of cognitive impairment may be heterogeneous. Little is known about neuropsychological treatment options. Preliminary evidence suggests cognitive symptoms may improve with cognitive training and naturally over time. In this clinical trial, we examined whether participation in a weekly group consisting of cognitive training and group psychotherapy is feasible and would exert beneficial effects on cognitive performance in PC and whether improvements were associated with intervention group participation or represented a temporal improvement effect during syndrome progression. 15 PC patients underwent an 8-week intervention. Cognitive performance was assessed before and after each intervention group participation. A control group of 15 PC patients with subjective neurocognitive or psychiatric complaints underwent two cognitive assessments with comparable time intervals without group participation. To attribute changes to the intervention group participation, interaction effects of group participation and time were checked for significance. This is an exploratory, non-randomized, non-blinded controlled clinical trial. Within the intervention group, significant improvements were found for most cognitive measures. However, significant time x group interactions were only detected in some dimensions of verbal memory and visuo-spatial construction skills. Significant time effects were observed for attention, concentration, memory, executive functions, and processing speed. The intervention setting was feasible and rated as helpful and relevant by the patients. Our results suggest that cognitive symptoms of PC patients may improve over time. Patients affected by both neurocognitive impairments and mental disorders benefit from group psychotherapy and neurocognitive training. The present study provides evidence for a better understanding of the dynamic symptomatology of PC and might help to develop further studies addressing possible therapy designs. The main limitations of this exploratory feasibility trial are the small sample size as well as the non-randomized design due to the clinical setting.

Breast Milk Application as a Natural Method for Umbilical Cord Care: A Community-Label 3-Arm Pilot Clinical Trial

Abstract Objective To compare the effects of human breast milk with those of chlorhexidine and the dry method on umbilical cord separation in Ethiopia. Methods This open-label 3-arm nonrandomized pilot clinical trial was conducted among 45 neonates (15 in each arm) with more than 630 home visits. After a standard cord cut, human breast milk, chlorhexidine, or nothing was applied once per day for 7 days. The primary outcome was the duration of cord separation, while the secondary outcomes were umbilical cord infection, neonatal fever, jaundice, feeding and breathing difficulty, and persistent crying. Results There were statistically significant differences in the time-to-cord separation between the human breast milk group and the chlorhexidine (P &lt; 0.001) and dry alone (P = 0.038) groups. Compared to those of chlorhexidine, the rates of cord separation among human breast milk and the dry-alone group were 16.02, with 95% confidence intervals (3.81, 37.43; P &lt; 0.001) and 3.15 (0.99, 10.00; P = 0.052), respectively. One (6.7%) cord site infection was observed in the dry-alone groups only. Conclusion This community-label study indicated that human breast milk application significantly shortened the length of umbilical cord separation time compared to chlorhexidine and dry methods. A large-scale randomized controlled trial is needed to confirm these results. Registration PACTR202310902873290; https://pactr.samrc.ac.za

Effect of Oral Zinc Supplementation on Phase Angle and Bioelectrical Impedance Vector Analysis in Duchenne Muscular Dystrophy: A Non-Randomized Clinical Trial

Zinc plays a crucial role in cell structure and functionality. Neurodegenerative Duchenne muscular dystrophy (DMD) alters muscle membrane structure, leading to a loss of muscle mass and strength. The objective of this study was to evaluate the changes in phase angle (PA) and bioelectrical impedance vector analysis (BIVA) results in patients with DMD after oral zinc supplementation. This clinical trial included 33 boys aged 5.6 to 24.5 years diagnosed with DMD. They were divided into three groups according to age (G1, G2, and G3) and supplemented with oral zinc. The mean serum zinc concentration was 74 μg/dL, and 29% of patients had concentrations below the reference value. The baseline values (mean (standard deviation)) of the bioelectrical impedance parameters PA, resistance (R), and reactance (Xc) were 2.59° (0.84°), 924.36 (212.31) Ω, and 39.64 (8.41) Ω, respectively. An increase in R and a decrease in PA and lean mass proportional to age were observed, along with a negative correlation (r = −0.614; p &lt; 0.001) between age and PA. The average cell mass in G1 was greater than that in G3 (p = 0.012). There were no significant differences in serum zinc levels or bioelectrical impedance parameters before and after zinc supplementation. We conclude that this population is at risk of zinc deficiency and the proposed dosage of zinc supplementation was not sufficient to alter serum zinc levels, PA and BIVA results.

Patient-Directed Education to Promote Deprescribing

Patient-directed educational materials are a promising implementation strategy to expand deprescribing reach and adoption, but little is known about the impact across medication groups with potentially different perceived risks. To examine the impact of a patient-directed education intervention on clinician deprescribing of potentially low-benefit (proton pump inhibitors) or high-risk medications (high-dose gabapentin, diabetes agents with hypoglycemia risks). This pragmatic multisite nonrandomized clinical trial took place at 3 geographically distinct US Veterans Affairs (VA) medical centers from April 2021 to October 2022. The total study sample was composed of the intervention cohort and the historical control cohort cared for by 103 primary care practitioners (PCPs). The primary intervention component was a medication-specific brochure, mailed during the intervention time frame to all eligible patients 2 to 3 weeks prior to upcoming primary care appointments. Patients seen by the same PCPs at the same sites 1 year prior to the study intervention served as controls. The primary binary outcome variable was deprescribing 6 months after the intervention, defined as complete cessation or any dose reduction of the target medication using VA pharmacy dispensing data. The total study sample included 5071 patients. The overall rate of deprescribing among the intervention cohort (n = 2539) was 29.5% compared with 25.8% among the controls (n = 2532). In an unadjusted model, the intervention cohort was statistically significantly more likely to have deprescribing (odds ratio [OR], 1.17 [95% CI, 1.03-1.33]; P = .02). In a multivariable logistic regression model nesting patients within PCPs within sites and controlling for patient and PCP characteristics, the odds of deprescribing in the intervention cohort were 1.21 times that of the control cohort (95% CI, 1.05-1.38; P = .008). The difference in deprescribing prevalence between the intervention and control cohorts (proton pump inhibitors: 29.4% vs 25.4%; gabapentin: 40.2% vs 36.2%; hypoglycemia risk: 27.3% vs 25.1%) did not statistically significantly differ by medication group (P = .90). This nonrandomized clinical trial found that patient-directed educational materials provided prior to scheduled primary care appointments can effectively promote deprescribing for potentially low-benefit and high-risk medication groups. ClinicalTrials.gov Identifier: NCT0429490.

Wearable Device–Based Intervention for Promoting Patient Physical Activity After Lung Cancer Surgery

ImportanceEmerging evidence suggests that wearable devices are feasible for monitoring physical activity among patients with lung cancer. However, the association between wearable devices and improvement in patient recovery after surgery remains underexplored.ObjectiveTo evaluate the effects of a wearable device intervention on the recovery of physical activity, cardiopulmonary function, and health-related quality of life (HRQOL) after lung cancer surgery.Design, Setting, and ParticipantsThis nonrandomized clinical trial with a historical control was conducted at a single tertiary cancer center (Samsung Comprehensive Cancer Center) in Seoul, South Korea, between October 18, 2018, and May 24, 2019. Patients were included if they had suspected or confirmed non–small cell lung cancer scheduled for curative surgery more extensive than lobectomy and had an Eastern Cooperative Oncology Group status of 0 or 1. Patients were compared with historical control participants from data collected between September 20, 2017, and September 10, 2018, as part of the Coordinated Approach to Cancer Patients’ Health for Lung Cancer (CATCH-LUNG) prospective cohort study. Data analysis was performed between June 21 and July 16, 2020.InterventionA personalized exercise regimen monitored via a wearable device was administered to intervention patients at home in 3 stages: preoperative (from diagnosis to surgery), immediate (from discharge to 2 months after surgery), and later postoperative (from 2 to 6 months after surgery). Control patients received usual care.Main Outcomes and MeasuresThe primary outcome was cardiopulmonary function, and the co–primary outcome was physical activity at 6 months after surgery, measured with 6-minute walking distance (6MWD) and number of daily steps, using a linear regression model. Secondary outcomes were changes in cardiopulmonary function, physical activity, and HRQOL, including function and symptoms from baseline to 2 weeks and 6 months after surgery. Additionally, cardiopulmonary function and physical activity (number of daily steps and time spent on moderate-to-vigorous physical activity [MVPA]) at 2 weeks after surgery, physical activity (time spent on MVPA) at 6 months after surgery, and HRQOL, including function and symptoms at 2 weeks and 6 months after surgery, were assessed as secondary outcomes.ResultsThis trial included 74 patients in the intervention group (mean [SD] age, 60.4 [8.7] years; 31 [41.9%] men and 43 [58.1%] women) and 120 in the control group (mean [SD] age, 60.2 [8.7] years; 65 [54.2%] men and 55 [45.8%] women). Daily steps, MVPA, and 6MWD decreased initially at 2 weeks after surgery but increased thereafter. The control group had a larger decrease in the number of daily steps from baseline compared with the intervention group (−4877 [95% CI, −5861 to −3893] steps vs −1753 [95% CI, −2968 to −539] steps) at 2 weeks after surgery. By 6 months after surgery, the intervention group increased their daily steps by 2220 (95% CI, 1006 to 3435) from baseline, whereas the control group did not return to their baseline number of steps. The intervention group had significantly more daily steps (12 321 [95% CI, 8749-15 761] vs 10 118 [95% CI, 7341-13 420]; P = .007) and had greater vigorous physical activity (33.6 [95% CI, 13.5 to 59.8] vs 18.5 [5.7 to 40.8] minutes; P = .003) at 6 months after surgery compared with the control group. No difference in 6MWD was found. However, the intervention group had better patient-reported physical function (mean [SD] score, 82.2 [17.3] vs 76.9 [17.5]; P = .04), less dyspnea (mean [SD] score, 24.8 [27.1] vs 34.5 [31.6]; P = .03), and less pain (mean [SD] score, 21.4 [20.2] vs 30.1 [26.8]; P = .01) at 2 weeks after surgery and less dyspnea (mean [SD] score, 5.4[12.4] vs 12[23.3]; P = .01) at 6 months after surgery compared with the control group.Conclusions and RelevanceIn this nonrandomized clinical trial, integration of perioperative exercise interventions using wearable devices improved physical activity (especially MVPA) and dyspnea at 6 months after lung cancer surgery compared with usual care. This finding suggests a promising role for wearable devices in personalizing perioperative rehabilitation strategies.Trial RegistrationClinicalTrials.gov Identifier: NCT03215537

Chimeric Antigen Receptor T Cells Targeting CD19 and GCC in Metastatic Colorectal Cancer

Chimeric antigen receptor (CAR) T-cell therapy (CART) has transformed the treatment landscape of hematologic cancer, but has negligible effects for adult solid cancers. In this trial, an autologous CAR T-cell product demonstrated antitumor activity in heavily pretreated patients with metastatic colorectal cancer (mCRC). To evaluate the safety and efficacy of guanylate cyclase-C (GCC19) CART in participants with metastatic colorectal cancer (mCRC). This single-arm, nonrandomized, phase 1 trial was conducted at the First Hospital of Jilin University from December 3, 2020, to April 13, 2022. Data analysis was conducted from May 2022 to April 2024. Adults with relapsed and refractory mCRC expressing GCC were treated with GCC19CART, a mixture of autologous CAR T cells transduced with lentiviral vectors expressing genes that encode either CD-19 CAR or GCC CAR. Safety and tolerability of CAR T-cell therapy targeting GCC in patients with mCRC without therapeutic options is capable of conferring a reasonable likeliness of clinical benefit. Other outcomes included objective response rate, progression-free survival, overall survival, and immune activation. Of 15 patients 9 (60%) were women, and the median (range) age was 44 (33-61) years. Treatment with GCC19CART was associated with the development of cytokine release syndrome and diarrhea in most patients, all of which were self-limited and manageable. The objective response rate was 40%, with a partial response in 2 of 8 and 4 of 7 patients treated with either 1 × 106 cells/kg or 2 × 106 cells/kg. Median overall survival was 22.8 months (95% CI, 13.4-26.1) at data cutoff; the median progress-free survival was 6.0 months in the high dose level group (95% CI, 3.0 to not available). The results of this nonrandomized clinical trial suggest that GCC19CART was safe and tolerable in heavily pretreated patients with mCRC and is the first CAR T-cell therapy known to produce objective clinical activity in refractory cancer. Given the paucity of effective therapeutics developed for colorectal cancer in recent decades, the observation that CD-19 CART target engagement can robustly induce GCC19CART target engagement sufficient to produce objective activity may serve as a foundation to develop effective cellular therapy in mCRC and other solid cancers. Chinese Clinical Trial Registry: ChiCTR2000040645.

Early experience using vacuum-assisted closure for managing soft tissue injuries in open type IIIB tibial fractures, a non-randomised controlled trial from a North African level one trauma centre

Purpose: The primary objective was to investigate our early results of using vacuum-assisted closure (VAC) for wound management in patients with open IIIB tibial fractures and compare the results with a group subjected to conventional daily dressing. Methods: A prospective non-randomised clinical trial (NRCT) with a parallel design and allocation ratio of 1:1 was conducted after obtaining ethical committee approval. Forty skeletally mature patients with unilateral type IIIB open tibia fractures were included over two years, starting from April 2019. In group A, patients were treated with VAC, which was changed every four days if needed, and in group B, patients had daily conventional dressings. Results: Both groups had no differences in the basic demographic, comorbidities, injury mechanism, and associated injuries. The need for secondary debridement surgeries was significantly lower in Group A than in Group B, 1 ± 0.50 versus 2.50 ± 0.85, respectively ( P &lt; 0.001). The time till definitive coverage was significantly lower in Group A than in Group B, 12.22 ± 2.90 versus 23.56 ± 8.68 (days); P &lt; 0.001. All coverage procedures succeeded in Group A, while four (20%) failed in Group B, P = 0.04. Infection was higher in Group B, with six (30%) patients compared to one (5%) in Group A, P = 0.01. Conclusion: Reports on VAC's role in managing severe open fracture wounds are rare in our area, and the initial results we obtained are encouraging, with lower infection rates and less cumbersome reconstruction procedures; however, further evaluation of the procedure's cost-effectiveness is mandatory.

Deviation parameters of intraoral scanning with and without artificial markers versus conventional impression of total, partial and congenital nasal defects: A pilot non-randomized clinical trial

PurposeThis pilot clinical trial aimed to investigate accuracy of intra-oral scanning (IOS) with and without artificial reference markers in capturing total, subtotal and congenital nasal defects. Basic proceduresThirteen patients with 3 types of nasal defects were selected and digitally scanned using an IOS with (ScM) and without artificial markers (Sc). Patients were grouped as follows; Group T (total nasal defect), Group P (partial/subtotal nasal defect), Group C (congenital defect). Silicone impressions of the defects were made and poured to get a model that was scanned using a Desktop scanner (Imp). The standard tessellation language (STL) files obtained from IOS were registered and compared to each other using a processing software. RMS, positive and negative average values were used to report deviations between the scans. Kruskal Wallis test was used to study the effect of defect type, while Friedmann was used to study the effect of impression technique. Results were considered significant at P≤.05. Main findingsAll deviation values showed statistically significant differences among the 3 studied nasal defects and among the 3 investigated impression techniques. The smallest deviation values were recorded in Sc-ScM of congenital defects (RMS= 0.13±0.04, +average=0.08±0.01, -average=-0.09±0.02), while the largest deviation values were recorded in IMP-Sc in the total defects (RMS= 0.38±0.05, +average=0.29±0.04, -average=-0.29±0.04). ConclusionsWithin the limitations of this study, it was concluded that the nasal defect type and the use of artificial markers during scanning affect the deviation parameters of the obtained scan. The combined effect of the studied parameters calls for the use of markers in when scanning total nasal defects.