Prospective Nonrandomized Clinical Trial Research Articles

Features of the quality of life of first graders taking into account gender differences and cognitive abilities

The purpose of the study: To study the features of the quality of life of first-graders, taking into account gender differences and cognitive abilities. Design: An open prospective non-randomized comparative clinical trial. Materials and methods: 631 children were examined, students of the first grades of secondary schools without a specialized bias № 110, 83, 75, 67, 9 Rostov-on-Don using the international questionnaire PedsQL 4.0 – Pediatric Quality of Life Inventory. To assess the cognitive development of children, the D. Wexler scale was used with the determination of the intellectual coefficient. Results: First-graders with a high level of cognitive development have reduced indicators of physical and emotional functioning, as well as the overall quality of life score. Girls with a high intellectual coefficient, in comparison with boys, have lower physical, emotional, school functioning and higher indicators of social functioning. The indicators of quality of life in children with a high level of cognitive development do not reflect the same in children who do "excellent". Conclusion: The revealed features of the quality of life of first-graders with different levels of cognitive development require differentiated medical, psychological and pedagogical support of children in this age period and further study of their health.

Results of the study of factors predicting the risk of the development of grade III radiation-induced mucositis during radiation or chemoradiation therapy in patients with oral cavity and oropharynx cancer.

Today, a number of methods and ways of prevention and treatment of radiation- -induced mucositis of the oral cavity and oropharynx have been developed, but the represented approaches are still not effective enough. Therefore, to increase the effectiveness of the prevention and treatment of radiation-induced mucositis, it is necessary to approach this problem comprehensively and individually, and to evaluate the factors affecting the development of mucositis. In this single-center prospective controlled non-randomized clinical trial, the results of clinical observation of the development of complications of radiation and chemoradiation therapy in 105 patients with a newly diagnosed squamous cell cancer of the oral cavity and oropharynx were analyzed. Factors affecting the risk of the development of grade III radiation-induced mucositis including the age, gender of the patients, their general condition before the treatment according to World Health Organisation scales, type of the treatment and its doses, additional use of immunotherapy with alpha/beta defensins, characteristic signs of the tumor process and all indices of the immune status of the patients before the treatment have been analyzed. The method of construction and analysis of one-factor logistic regression models, where 24 indices were analyzed as factorial features, showed that the reduction of the risk of the development of grade III radiation-induced mucositis is predicted by several factors: immunotherapy, gender, serum concentrations of IgG and IgA. A decrease (P < 0.001) in the risk of the development of grade III radiation-induced mucositis was revealed if immunotherapy with alpha/beta defensins (with a total dose of 40 mg) was included into the treatment scheme (relative odds (RO) 0.05; 95% reference interval (RI) 0.02-0.18), in comparison with patients of the groups where it was not present or this immune agent was used in a total dose of 60 mg (P = 0.001, RO 0.06; 95% RI 0.01-0.30). The next factorial sign was gender, namely the risk of the development of grade III radiation-induced mucositis was lower for men (P = 0.003; RO 0.15; 95% RI 0.04-0.53) compared to women. An increase (P = 0.024) in the risk of the development of grade III radiation-induced mucositis with an increase in the initial level of IgG serum concentration was revealed, (RO 1.08; 95% RI 1.01-1.16) for each 1 mg/mL, as well as an increase (P = 0.044) in the possibility of the appearance of grade III radiation-induced mucositis with an increase in the serum concentration of IgA (RO 1.23; 95% RI 1.01-1.50) for every 1 mg/mL also before the beginning of the treatment. Multifactorial analysis has also confirmed that the risk of the development of grade III radiation-induced mucositis increases (P = 0.008) with a high serum IgG concentration before the treatment or with an increase in this index during therapy (RO 1.13; 95% RI 1.03-1.09) for every 1 mg/mL (when standardized by other risk factors). It was determined that when standardizing according to other factors (gender, IgG level), the risk of the development of grade III radiation-induced mucositis in the use of the immune agent alpha/beta defensins in a total dose of 40 mg per course decreases (P < 0.001; RO 0.08; 95% RI 0.02-0.27) compared to patients with oral cavity and oropharynx cancer who were not treated with immunotherapy. The risk of the development of grade III radiation-induced mucositis also decreases (P = 0.001) in the use of immunotherapy in a higher dose, i.e. 60 mg per course (RO 0.03; 95% RI 0.004-0.24 compared to patients whose treatment did not include immunotherapy (when standardized by other factors). As a result of this controlled clinical study, some factors were determined in addition to the radiation as those affecting the risk of the development of grade III radiation-induced mucositis in patients with oral cavity and oropharynx cancer during special treatment. These factors comprise the inclusion of immunotherapy with alpha/beta defensins into the specific treatment; gender, and baseline levels of serum IgG and IgA concentrations suggest a pattern in which the higher the serum IgG and IgA concentrations are before the start of the treatment, the greater is the likelihood of severe radiation-induced mucositis degree during special therapy. The results of the study of humoral state of the immune system in patients with oral cavity and oropharynx cancer before the beginning of chemoradiation therapy can be used as prognostic risk factors for the development of severe gamma-irradiation-induced mucositis of the oropharyngeal area, as well as an indication for the use of immunotherapeutic agents (in particular, alpha/beta defensins) that are able to polarize the immune response towards type 1 T-helpers through their immunomodulatory action.

CUPCOMP: A multi-site UK trial in carcinoma of unknown primary: A comparison across tissue and liquid biomarkers.

3059 Background: Cancer of Unknown Primary (CUP) is a difficult to treat cancer entity for which the tumour origins remain elusive. There is emerging evidence to support a precision medicine approach to aid treatment decisions, however scarcity of tumour tissue for molecular profiling remains a challenge. CUPCOMP sought to compare the feasibility of molecular profiling from both tissue and blood in patients (pts) diagnosed with CUP. Methods: A non-randomised prospective feasibility clinical trial conducted across 7 UK sites between 06/2021-02/2023. Eligible pts had a histological confirmed diagnosis of favourable/unfavourable CUP based on clinical, radiological, and pathological review at a CUP Multi-Disciplinary Team meeting and ESMO Guidelines for CUP. Pts had mutation profiling performed from circulating tumour DNA (ctDNA) (FoundationOne Liquid CDx) and tumour tissue (FoundationOne CDX or whole genome sequencing (WGS)). All results were discussed at a dedicated Molecular Tumour Board (MTB) to evaluate the activation state of oncogenic pathways. Results: Baseline characteristics of the 117 pts recruited are shown (Table). 114/117 (97%) pts had successful blood (109/117; 93% pts) or tissue (69/117; 59% pts) molecular profiling; both methods were performed in 64/117 (55%) pts. WGS was only successful in 15/21 pts where repeat biopsy was obtained. Where targeted tissue and blood profiling was performed using the same panel (49/117; 42%): 421/550 (77%) Single Nucleotide Variants (SNVs) found in tissue were concordant in ctDNA. ctDNA tumour fraction was ≥10% in 41/109 (35%) pts. In ctDNA, 1556 SNVs, across 271 genes, and 42 rearrangements were identified. 73/114 (64%) of cases carried an actionable alteration in blood or tissue, as determined by MTB. The most frequently reported actionable gene alterations were: KRAS (n=11; 10%); ATM (n=9; 8%); ARID1A (n=9; 8%); PIK3CA (n=10; 9%); NF2 (n=7; 6%); BRAF (n=7; 6%); FGFR2-fusion (n=7; 6%). A tumour mutational burden (TMB) of ≥10 mutations/Mb was detected in 25/117 (22%) of pts. Potential germline variants were found in 8% of pts. 80/114 (70%) pts were alive 6 months after consent to trial. Conclusions: Successful tissue-based molecular profiling is challenging in pts with CUP; achieved in only 59% of pts in this cohort. ctDNA analysis was feasible (93% successful) and reliably concordant with tissue. Potentially actionable alterations were found in 64% of pts. ctDNA molecular profiling should be considered as a reliable alternative to tissue-based testing in pts diagnosed with CUP. Clinical trial information: NCT04750109 . [Table: see text]

Comparing Magnetic Resonance Imaging and Prostate-Specific Membrane Antigen-Positron Emission Tomography for Prediction of Extraprostatic Extension of Prostate Cancer and Surgical Guidance: A Prospective Nonrandomized Clinical Trial.

Survivors of surgically managed prostate cancer may experience urinary incontinence and erectile dysfunction. Our aim was to determine if 68Ga-prostate-specific membrane antigen-11 positron emission tomography CT (PSMA-PET) in addition to multiparametric (mp) MRI scans improved surgical decision-making for nonnerve-sparing or nerve-sparing approach. We prospectively enrolled 50 patients at risk for extraprostatic extension (EPE) who were scheduled for prostatectomy. After mpMRI and PSMA-PET images were read for EPE prediction, surgeons prospectively answered questionnaires based on mpMRI and PSMA-PET scans on the decision for nerve-sparing or nonnerve-sparing approach. Final whole-mount pathology was the reference standard. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic curves were calculated and McNemar's test was used to compare imaging modalities. The median age and PSA were 61.5 years and 7.0 ng/dL. The sensitivity for EPE along the posterior neurovascular bundle was higher for PSMA-PET than mpMRI (86% vs 57%, P = .03). For MRI, the specificity, positive predictive value, negative predictive value, and area under the curve for the receiver operating characteristic curves were 77%, 40%, 87%, and 0.67, and for PSMA-PET were 73%, 46%, 95%, and 0.80. PSMA-PET and mpMRI reads differed on 27 nerve bundles, with PSMA-PET being correct in 20 cases and MRI being correct in 7 cases. Surgeons predicted correct nerve-sparing approach 74% of the time with PSMA-PET scan in addition to mpMRI compared to 65% with mpMRI alone (P = .01). PSMA-PET scan was more sensitive than mpMRI for EPE along the neurovascular bundles and improved surgical decisions for nerve-sparing approach. Further study of PSMA-PET for surgical guidance is warranted in the unfavorable intermediate-risk or worse populations. NCT04936334.

Safety profile and effects on the peripheral immune response of fecal microbiota transplantation in clinically healthy dogs.

Fecal microbiota transplantation (FMT) is increasingly used for gastrointestinal and extra-gastrointestinal diseases in veterinary medicine. However, its effects on immune responses and possible adverse events have not been systematically investigated. Determine the short-term safety profile and changes in the peripheral immune system after a single FMT administration in healthy dogs. Ten client-owned, clinically healthy dogs as FMT recipients, and 2 client-owned clinically healthy dogs as FMT donors. Prospective non-randomized clinical trial. A single rectal enema of 5 g/kg was given to clinically healthy canine recipients. During the 28 days after FMT administration, owners self-reported adverse events and fecal scores. On Days 0 (baseline), 1, 4, 10, and 28 after FMT, fecal and blood samples were collected. The canine fecal dysbiosis index (DI) was calculated using qPCR. No significant changes were found in the following variables: CBC, serum biochemistry, C-reactive protein, serum cytokines (interleukins [IL]-2, -6, -8, tumor necrosis factor [TNF]-α), peripheral leukocytes (B cells, T cells, cluster of differentiation [CD]4+ T cells, CD8+ T cells, T regulatory cells), and the canine DI. Mild vomiting (n = 3), diarrhea (n = 4), decreased activity (n = 2), and inappetence (n = 1) were reported, and resolved without intervention. Fecal microbiota transplantation did not significantly alter the evaluated variables and recipients experienced minimal adverse events associated with FMT administration. Fecal microbiota transplantation was not associated with serious adverse events, changes in peripheral immunologic variables, or the canine DI in the short-term.

4-week results of “Linni Slim” synbiotic in patients with metabolic syndrome

The purpose of the study is to evaluate the efficacy and safety of a synbiotic in a short-term course (4 weeks), including an extract of garcinia cambogia, probiotics and prebiotics in patients with MS Materials and methods. The pilot, observational, open-label, non-randomized prospective clinical trial included 20 patients with metabolic syndrome (13 males and 7 females, Me age 42 years). A biologically active food supplement (synbiotic) “LINNI SLIM” (PharmlandBIO, Republic of Belarus) was used, including an extract of garcinia cambogia (containing 60% hydroxycitric acid, 0.03 g/g), probiotic strains of the genus Bifidobacterium (B. bifidum, B. animalis ssp lactis, B. longum ssp longum) CFU/g) - 0.066x 109 CFU/g and Lactobacillus (L. Acidophilus, L. Plantarum, L. Rhamnosus, L. Casei, L. Crispatus, L. Reuteri, L. Gasseri) - 0,134 x 109 CFU/g; prebiotics (psyllium husk, microcrystalline cellulose, linseed fiber, inulin, fenugreek). The daily dose of garcinia cambogia is 0.3 g, dietary fiber is 5.16 g. The parameters of nutritional (including bioimpedance analysis) and metabolic status, safety (hepatotoxic effects) and tolerability (gastrointestinal symptoms, 2H-breath test with lactulose and glucose) were evaluated. Results. There was a significant decrease in serum concentrations of insulin (15.2 [9.7; 23.0] Vs 10.9 [6.6; 16.4] mcU/ml; p=0.002), triglycerides (2.1 [1.4; 2.3] Vs 1.2 [1.2; 1.9] mmol/l; p=0.002), values of the HOMA-IR index (3.77 [2.54; 6.08] Vs 2.50 [1.44; 3.65]; p=0.003) without deviation of serum biomarkers of liver damage. Good tolerability and safety of “LINNI SLIM” was established: the appearance of symptoms of dyspepsia, stool disorders requiring the abolition of dietary supplements, deviations in the results of the 2H-breath test were not registered. Conclusion. A 4-week course of using the “LINNI SLIM” synbiotic at a daily dose of 10 grams has a positive effect on the metabolic status of the body (reduction of insulin, triglycerides, HOMA-IR - insulin resistance index) with satisfactory safety parameters. The effectiveness and improvement of “metabolic health” allows the use of the “LINNI SLIM” synbiotic in the initial therapy for reducing (controlling) body weight in people suffering from metabolic syndrome on the background of obesity.

Effectivity and safety of trifocal intraocular lenses and capsular tension rings implantation for cataract patients with axial high myopia.

To assess effectivity and safety of trifocal intraocular lenses (IOLs) and capsular tension rings in treating cataract patients with axial high myopia. A prospective nonrandomized controlled clinical trial was conducted. Totally 98 eyes (74 patients) who underwent femtosecond laser-assisted cataract surgery (FLACS) with trifocal IOLs were enrolled in the study and followed up for 2y after surgery: 46 eyes (33 patients) with capsular tension ring implantation in the long axial lengths (AL) group (26<AL<29 mm) and 52 eyes (41 patients) in the normal AL group (22<AL<24.5 mm). Postoperative outcomes about effectivity and safety, including the subjective and objective visual quality, and postoperative complications were assessed. Uncorrected distance visual acuity at 5 m and uncorrected intermediate visual acuity at 60 and 80 cm in the long AL group were significantly worse than those in the normal AL group at 3mo postoperatively (P<0.05). The differences in reading speed, spectacle independence and potential visual complaints between the two groups were not statistically significant (P>0.05). The dysfunctional lens index and total modulation transfer function (MTF) average height were similar between the two groups. The postoperative internal coma aberrations in the axial high myopia eyes were significantly higher than that in the normal AL group (P<0.05). The total satisfaction score in the long AL group (91.32±2.76) was slightly higher than that in the normal AL group (90.36±3.47), but there was no difference (P=0.136). A statistically negative correlation was found between corrected distance visual acuity (CDVA) and dysfunctional lens index (r=-0.382, P=0.009), and between CDVA and the total MTF average height (r=-0.374, P=0.01). But there was no significant correlation between CDVA and total satisfaction score (r=0.059, P=0.696). Postoperative complications mainly presented as posterior capsular opacity (PCO), retinal detachment and cystoid macular edema. There was no difference in the incidence of fundus disease (6.5% vs 3.8%, P=0.663) or PCO (17.4% vs 7.7%, P=0.217) between the two groups at two years. The utilization of trifocal IOL and capsular tension ring implantation is beneficial for cataract patients with axial high myopia undergoing FLACS. This approach not only ensures excellent subjective feelings and objective visual quality, but also does not increase the incidence of postoperative complications.

Complications and Patient-Centered Outcomes of an Implant- Supported Single Crown after Immediate and Delayed Loading: A Systematic Review and Meta-analysis.

Single implants are a predictable treatment, and immediate loading can be an option with acceptable survival rates. Clinical and patient-centered outcomes comparing immediate and delayed protocol of single implants are unclear. The purpose of this study was to assess complications, satisfaction, and quality of life of patients rehabilitated with delayed and immediate loading single crowns. An electronic search was conducted in PubMed/MEDLINE, Scopus, Web of Science, Cochrane Library, and Embase databases up to February 2023. Only prospective studies, randomized and non-randomized clinical trials comparing immediate and delayed loading were included. For the quantitative analysis, dichotomous and continuous variables were evaluated with a 95% confidence interval. A total of 20 studies were evaluated. No statistically significant difference between protocols was observed: satisfaction (I2: 0%; P = 0.42), quality of life (I2: 0 %; P = 0.05), biological complications (I2: 9%; P = 0.17) mechanical complications (I2: 58%; P = 0.84), and survival rate (I2: 0%; P = 0.38). Subgroup analysis showed significant differences only for marginal bone loss when immediate implants were placed in the mandible (IÇ: 15%; P = 0.01) and posterior zone (I2: 0%; P = 0.001). Complications and patient-centered outcomes for immediate single-implant crowns were comparable to delayed loading. Scientific evidence showed no significant difference between loading protocols for survival rates. Although several factors could interfere with the complication events, implant failures, and marginal bone loss, the subgroup analysis evidenced that only immediate implants placed in the posterior mandible zone had higher statistically significant mean marginal bone loss.

Lumpectomy without radiation for ductal carcinoma in situ of the breast: 20-year results from the ECOG-ACRIN E5194 study

We report the 20-year rate of ipsilateral breast event (IBE) for patients with ductal carcinoma in situ (DCIS) treated with lumpectomy without radiation on a non-randomized prospective clinical trial. Patients were enrolled in cohort 1: low- or intermediate-grade DCIS, size ≤ 2.5 cm (n = 561); or cohort 2: high-grade DCIS, size ≤ 1 cm (n = 104). The Kaplan–Meier method was used to estimate time-to-event distributions. Cox proportional hazard methods were used to estimate hazard ratios (HRs) and tests for significance for event times. 561 patients were enrolled in cohort 1 and 104 in cohort 2. After central pathology review, 26% in cohort 1 were recategorized as high-grade and 26% in cohort 2 as low- or intermediate-grade. Mean DCIS size was similar at 7.5 mm in cohort 1 and 7.8 mm in cohort 2. Surgical margin was ≥3 mm in 96% of patients, and about 30% received tamoxifen. Median follow-up was 19.2 years. There were 104 IBEs, of which 54 (52%) were invasive. The IBE and invasive IBE rates increased in both cohorts up to 15 years, then plateaued. The 20-year IBE rates were 17.8% for cohort 1 and 28.7% for cohort 2 (p = 0.005), respectively. Invasive IBE occurred in 9.8% and 15.1% (p = 0.09), respectively. On multivariable analysis, IBE risk increased with size and was higher in cohort 2, but grade and margin width were not significantly associated with IBE. For patients with DCIS treated with excision without radiation, the rate of IBE increased with size and assigned cohort mostly in the first 15 years.

Real-Time Machine Learning Alerts to Prevent Escalation of Care: A Nonrandomized Clustered Pragmatic Clinical Trial.

Machine learning algorithms can outperform older methods in predicting clinical deterioration, but rigorous prospective data on their real-world efficacy are limited. We hypothesized that real-time machine learning generated alerts sent directly to front-line providers would reduce escalations. Single-center prospective pragmatic nonrandomized clustered clinical trial. Academic tertiary care medical center. Adult patients admitted to four medical-surgical units. Assignment to intervention or control arms was determined by initial unit admission. Real-time alerts stratified according to predicted likelihood of deterioration sent either to the primary team or directly to the rapid response team (RRT). Clinical care and interventions were at the providers' discretion. For the control units, alerts were generated but not sent, and standard RRT activation criteria were used. The primary outcome was the rate of escalation per 1000 patient bed days. Secondary outcomes included the frequency of orders for fluids, medications, and diagnostic tests, and combined in-hospital and 30-day mortality. Propensity score modeling with stabilized inverse probability of treatment weight (IPTW) was used to account for differences between groups. Data from 2740 patients enrolled between July 2019 and March 2020 were analyzed (1488 intervention, 1252 control). Average age was 66.3 years and 1428 participants (52%) were female. The rate of escalation was 12.3 vs. 11.3 per 1000 patient bed days (difference, 1.0; 95% CI, -2.8 to 4.7) and IPTW adjusted incidence rate ratio 1.43 (95% CI, 1.16-1.78; p < 0.001). Patients in the intervention group were more likely to receive cardiovascular medication orders (16.1% vs. 11.3%; 4.7%; 95% CI, 2.1-7.4%) and IPTW adjusted relative risk (RR) (1.74; 95% CI, 1.39-2.18; p < 0.001). Combined in-hospital and 30-day-mortality was lower in the intervention group (7% vs. 9.3%; -2.4%; 95% CI, -4.5% to -0.2%) and IPTW adjusted RR (0.76; 95% CI, 0.58-0.99; p = 0.045). Real-time machine learning alerts do not reduce the rate of escalation but may reduce mortality.

Multidimensional 3D-Printed Scaffolds and Regeneration of Intrabony Periodontal Defects: A Systematic Review.

The utilization of regenerative techniques in periodontology involves tailoring tissue engineering principles to suit the oral cavity's unique environment. Advancements in computer-assisted technology, specifically utilizing cone beam computed tomography (CBCT), enabled the fabrication of 3D-printed scaffolds. The current review aims to explore whether 3D-printed scaffolds are effective in promoting osteogenesis in patients with periodontal defects. A thorough exploration was undertaken across seven electronic databases (PubMed, Scopus, ScienceDirect, Google Scholar, Cochrane, Web of Science, Ovid) to detect pertinent research in accordance with specified eligibility criteria, aligning with the PRISMA guidelines. Two independent reviewers undertook the screening and selection of manuscripts, executed data extraction, and evaluated the bias risk using the Newcastle-Ottawa Scale for non-randomized clinical trials and SYRCLE's risk of bias tool for animal studies. Initially, 799 articles were identified, refined by removing duplicates. After evaluating 471 articles based on title and abstract, 18 studies remained for full-text assessment. Eventually, merely two manuscripts fulfilled all the eligibility criteria concerning human trials. Both studies were prospective non-randomized clinical trials. Moreover, 11 animal studies were also included. The use of multidimensional, 3D-printed, customized scaffolds appears to stimulate periodontal regeneration. While the reported results are encouraging, additional studies are required to identify the ideal characteristics of the 3D scaffold to be used in the regeneration of periodontal tissue.

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.

Two-Year Myopia Management Efficacy of Extended Depth of Focus Soft Contact Lenses (MYLO) in Caucasian Children

To evaluate the progression of myopia as assessed by change in axial length (AL) and spherical equivalent (SE) from baseline in Caucasian children wearing extended depth of focus soft contact lenses (CLs) compared to distance single-vision spectacles. Prospective non-randomized comparative clinical trial. A total of 90 children (6-13 years of age) with SE ranging from -0.75 to -10.00 diopters (D) were recruited. Of these children, 45 were fitted with CLs (MYLO, mark´ennovy), whereas 45 children wore spectacles. Cycloplegic refraction was measured with an auto-refractometer (Topcon-TRK-2P) and AL with an IOLMaster-700 (Zeiss) at 6-month intervals. Subjective responses after 1 month of CL wear related to vision and comfort were determined using a questionnaire with a scale from 1 (very poor) to 10 (excellent). High-contrast visual acuity (HCVA) and contrast sensitivity (CS) were evaluated at baseline, 12, and 24 months. After 2 years, mean change in SE/AL in the CL group was -0.62 ± 0.30 D/0.37 ± 0.04 mm and -1.13 ± 0.20 D/0.66 ± 0.03 mm in the spectacles group (P < .001). Cumulative absolute reduction in axial elongation (CARE) was 0.29 ± 0.06 mm. Difference in SE change was -0.50 ± 0.34 D. Although 100% of CL group had an AL increase ≤0.50 mm, all participants increased ≥0.50 mm in the spectacles group. In all, 53% of the CL group and 1% in the spectacles group showed a progression in SE ≤ -0.50D. All questionnaire items showed a mean value ≥9. There was a reduction logMAR HCVA in the CL compared to the spectacles group but it was less than 1 line (P < .001). Use of MYLO CLs reduced axial elongation and myopia progression compared to use of distance single-vision spectacles.

Logistic regression model for predicting failure of dual antihypertensive therapy: a prospective comparative non-randomized clinical trial

Background. Initial dual antihypertensive therapy is currently considered as the first management step for the majority of patients with arterial hypertension. However, it often fails to achieve the target blood pressure levels. An approved algorithm for predicting the failure of dual antihypertensive therapy is still to be developed. Objectives. To establish predictors of dual antihypertensive therapy failure in patients with high and very high cardiovascular risk and to create a model for predicting negative outcome of dual antihypertensive therapy. Methods. The paper presents a prospective comparative non-randomized clinical trial. The recruiting of participants and recording of results were carried out in March–December 2019 with 3 months of the follow-up period. The trial involved examination of 88 patients with poor blood pressure control, stage II and III arterial hypertension, high and very high cardiovascular risk of stages 1–3. Clinical and laboratory examination was carried out in compliance with the current regulatory documents. Additional examination included tests for uric acid, high-sensitivity C-reactive protein, as well as respiratory polygraphy and computerized capillaroscopy. All patients were prescribed dual antihypertensive therapy. The primary search for predictors was performed using the binary logistic regression. The predictive model was developed by stepwise variable selection. The diagnostic significance of the binary classifier was assessed by means of ROC-curve analysis; the calculation was performed using MedCalc 20.218 software (MedCalc Software Ltd., Belgium). Results. Administration of two hypotensive drugs appears to be effective in 33% of patients. The final model for predicting negative outcomes of dual antihypertensive therapy included such independent predictors as interventricular septal thickness, daily mean systolic blood pressure, and area density of the capillary network. The odds ratio accounted for 9.1 (95% confidence interval 3.12; 26.82). The area under the ROC curve based on the multiple binary logistic regression model comprised 0.805±0.05 with 95% confidence interval: 0.707-0.882 (p&lt;0.0001). The sensitivity and specificity of the method amounted to 83.1 and 69.0%, respectively. The prediction accuracy comprised 77.3%. Conclusion. The development of patient-oriented algorithms for selection of hypotensive treatment is considered to be essential due to poor blood pressure control during dual antihypertensive therapy. The developed prognostic model may be applied when managing hypertension.

FRI608 Secondary Prevention Of Diabetes Type 1 With Oral Calcitriol And Analogs, The Precal Study

Abstract Disclosure: D.T. Papadimitriou: None. E. Dermitzaki: None. P. Christopoulos: None. M. Papagianni: None. K. Kleanthous: None. C. Marakaki: None. A. Papadimitriou: None. G. Mastorakos: None. Type 1 diabetes (T1D) hits about 1:300 with rising incidence affecting increasingly younger children. Population screening at ages 2 and 6 yrs with T1D associated autoantibodies (T1Ab) has been recently proven sensitive. While potential treatments to prevent or delay T1D are currently in development, a population based cost-effective preventive strategy is still lacking. Hence, 2000 IU cholecalciferol daily in a large birth cohort study published in 2001 reduced by 80% the risk of T1D in 1 yr. A pilot clinical trial 10 yrs ago, demonstrated negativation of T1Ab within 0.6 (0.4-2.1) yrs under oral calcitriol in 12 children. To further pursue this hypothesis, we initiated a prospective interventional non-randomized clinical trial, the PRECAL study (ISRCTN17354692). Between 2010-2022, 50 children (26 boys, 24 girls) aged 0.65-16,37 yrs identified as at high risk for T1D were included: 44 were positive for T1Ab (Insulin auto-antibodies, IAA; anti-tyrosinase abs, IA2, anti-glutamic decarboxylase abs, GAD; islet auto-abs, ICA; anti-Zn8 if available) and 6 with negative T1Abs had predisposing HLA A DQ DR haplotypes and genotypes. Nine were diagnosed with varied impaired glucose tolerance (IGT) ( all T1Ab+), 4 with pre-T1D (3 T1Ab+ and 1 HLA+), and 9 had new-onset T1D (all T1Ab+). Serum T1Ab levels and fasting plasma glucose, HbA1c, c-peptide, Ca (tolerated ≤11.5 mg/dl), P, ALP, Ca/Cr 2-hr urine morning sample, 25(OH)D, 1-25(OH)2D with renal ultrasound in cases with hypercalcemia/hypercalciuria (tolerated ≤50%, or at the upper normal for age) were determined before and q3-6 months after initiation of calcitriol (0.05 mcg/Kg/day) 0.25-0.5 x 1-3/day or its synthetic analogue, paricalcitol (thrice the calcitriol dose) 1-4 mcg x 1-3/day p.o. under cholecalciferol repletion. Measurements are given as median and range. Available data on 42 (7 dropouts, 1 follow-up &amp;lt; 3 m). All 26 without pre-T1D/T1D followed 3.06 (0.5-10) yrs negativized T1Ab (15 IAA, 3 IA2, 4 ICA, 2 GAD, 1 IAA/GAD, 1 ICA/GAD) within 0.57 (0.32-1.3) yrs or did not progress to T1D [5 +HLA, follow-up 3 (1-4) yrs]. From 4 pre-T1D, 1 negativized T1Ab (follow-up 1 yr), 1 with +HLA did not progress to T1D (follow-up 3.3 yrs) and 2 with +T1Ab developed T1D in 6m/3yrs. Three out of 8 children with T1D at presentation progressed immediately to overt disease, 5 showed complete remission for 1 yr (1m-2yrs). Five with +T1Ab relapsed and negativized again after resuming therapy. Four (aged &amp;lt; 3 yrs) negativized anti-TPO/TG, and 2 anti-transglutaminase-IgA. Eight presented mild hypercalciuria/hypercalcemia, resolving with dose titration/discontinuation. Calcitriol, and it’s less-calcemic analogue paricalcitol were 100% effective and reasonably safe in negativizing T1Ab in healthy children, possibly preventing the otherwise probably inevitable evolution towards clinical development of T1D, at least if started soon enough after seroconversion. Presentation: Friday, June 16, 2023

Enhanced efficacy of a novel aspirator in uniportal video-assisted thoracoscopic mediastinal lymph node dissection: a non-randomized prospective clinical trial.

Video-assisted thoracoscopic surgery (VATS) is the standard approach in early-stage non-small cell lung cancer (NSCLC) and surgical aspirators play a crucial role. Traditional aspirators lack the ability to pull and lift tissue and cannot achieve optimal exposure. Therefore, we designed a new surgical aspirator that combined the function of thoracoscopic forceps. In this study, we aimed to validate the efficacy and safety of this new surgical aspirator. We performed a prospective non-randomized intervention trial and enrolled 504 consecutive patients scheduled for uniportal VATS in early NSCLC requiring mediastinal lymph node dissection. A novel aspirator we developed with a clamping function via a front pliers-like structure was implemented in intervention group, whereas traditional aspirator was used in control group. Time spent for nodal dissection in No. 2/4R and No. 7R/L (No. 7 lymph nodes resected through right or left side) lymph nodes and perioperative adverse events related to lymph node dissection were recorded. Mann-Whitey U test was applied to analyze sex and pathological type, an independent-samples t-test was applied to analyze surgery time and age. In total, 250 of enrolled patients were allocated into traditional aspirator group and 254 of them were allocated into new aspirator group. Surgeons spent 544.71±120.80 (range, 332-917, median 541) seconds dissecting No. 2/4R lymph nodes with traditional aspirators and 507.54±100.00 (range, 348-702, median 520) seconds dissecting with new aspirators (P=0.008). The traditional aspirator group had an average surgery time of 507.11±104.61 (range, 310-785, median 510) seconds for No. 7R lymph nodes and 608.47±128.50 (range, 397-919, median 606) seconds for No. 7L lymph nodes, while that in the new aspirator group was 465.09±94.94 (range, 271-744, median 476) seconds (P=0.001) and 549.39±102.11 (range, 368-782, median 538) seconds (P<0.001). The new aspirator showed an efficacy advantage in mediastinal lymph node dissection in VATS, without additional risk. This is the first report about a new suction device combining the functions of both traditional surgical aspirators and forceps, which can effectively shorten the time of mediastinal lymph node dissection and improve the efficiency of thoracoscopic surgery without increasing lymph node dissection-related adverse events.

Effect of Adjuvant Chemotherapy in Highly Malignant Non-Metastatic Prostate Cancer: An Interim Analysis of Non-Randomized Comparative Trials.

Gleason grade group 5 (GG5) prostate cancers is aggressive with high metastatic rates and is not sensitive to androgen deprivation therapy (ADT). Even the presence of a limited (tertiary) Gleason pattern 5 component may have high aggressive biological behavior. This study aims to prospectively evaluate whether a non-androgen receptor pathway therapy - adjuvant chemotherapy could improve clinical outcomes among non-metastatic prostate cancer with the above highly malignant characters. This prospective non-randomized clinical trial included non-metastatic prostate cancer patients with pathologically proven Gleason score of 9-10 or tertiary Gleason pattern 5. Each subject was allowed to decide whether to receive four to six cycles chemotherapy of docetaxel after receiving a standard treatment (i.e., radical surgery ± radiotherapy or radical radiotherapy combined with long-term ADT). The primary endpoint was event-free survival (EFS). Event was defined as any of biochemical failure or imaging failure, or change of systemic therapy due to PSA arises, or death. The secondary end points were distant metastasis-free survival (MFS), overall survival (OS), and treatment-related adverse events. A total of 188 consecutive patients were enrolled from November 2019 to November 2022. Median prostate-specific antigen was 26.6 ng/ml. 52% had T3b to T4 disease, 27% had N1 disease. 140 patients received standard therapy only, and 48 patients received adjuvant chemotherapy after radical therapy. The median follow-up time was 18.4 (3.0-36.7) months. The estimated 36-month EFS of the chemotherapy group and the control group were 94.7% vs. 72.8% (p = 0.044). There were 1 event who added novel endocrine therapy in the chemotherapy group, and 21 events in the control group, including 6 cases of biochemical recurrence and 9 cases of lymph node and distant metastasis, 4 cases that changed systemic therapy and 2 cases died. The MFS of the two groups at 36 months were 100% and 90.7%, respectively (P = 0.143). After the 1:1 propensity score match, the EFS and MFS of the two groups were 94.7% and 80.8% (P = 0.069), and 100% and 93.1% (P = 0.132), respectively. The urinary toxicity of grade 2 and 3 in the chemotherapy group and the control group were 4.2% and 7.1% (P = 0.134) while the grade 2 rectal toxicity were 5.0% and 10.4% (P = 0.317), respectively. No grade 4 toxicity occurred. Considering the chemotherapy-related side effects, grade 3 or above toxicity were leukopenia (41.7%), alopecia (27.1%), thrombocytopenia (2.1%) and edema (2.1%). Results of this interim analysis shows that the addition of adjuvant chemotherapy after standard radical therapy tends to improve the overall recurrence and metastasis free survival of patients with highly malignant prostate cancer, and the adverse effects are tolerable, which should be confirmed by long-term follow-up results.

Quality and transparency of evidence for implantable cardiovascular medical devices assessed by the CORE-MD consortium.

The European Union Medical Device Regulation 2017/745 challenges key stakeholders to follow transparent and rigorous approaches to the clinical evaluation of medical devices. The purpose of this study is a systematic evaluation of published clinical evidence underlying selected high-risk cardiovascular medical devices before and after market access in the European Union (CE-marking) between 2000 and 2021. Pre-specified strategies were applied to identify published studies of prospective design evaluating 71 high-risk cardiovascular devices in seven different classes (bioresorbable coronary scaffolds, left atrial appendage occlusion devices, transcatheter aortic valve implantation systems, transcatheter mitral valve repair/replacement systems, surgical aortic and mitral heart valves, leadless pacemakers, subcutaneous implantable cardioverter-defibrillator). The search time span covered 20 years (2000-21). Details of study design, patient population, intervention(s), and primary outcome(s) were summarized and assessed with respect to timing of the corresponding CE-mark approval. At least one prospective clinical trial was identified for 70% (50/71) of the pre-specified devices. Overall, 473 reports of 308 prospectively designed studies (enrolling 97 886 individuals) were deemed eligible, including 81% (251/308) prospective non-randomized clinical trials (66 186 individuals) and 19% (57/308) randomized clinical trials (31 700 individuals). Pre-registration of the study protocol was available in 49% (150/308) studies, and 16% (48/308) had a peer-reviewed publicly available protocol. Device-related adverse events were evaluated in 82% (253/308) of studies. An outcome adjudication process was reported in 39% (120/308) of the studies. Sample size was larger for randomized in comparison to non-randomized trials (median of 304 vs. 100 individuals, P < .001). No randomized clinical trial published before CE-mark approval for any of the devices was identified. Non-randomized clinical trials were predominantly published after the corresponding CE-mark approval of the device under evaluation (89%, 224/251). Sample sizes were smaller for studies published before (median of 31 individuals) than after (median of 135 individuals) CE-mark approval (P < .001). Clinical trials with larger sample sizes (>50 individuals) and those with longer recruitment periods were more likely to be published after CE-mark approval, and were more frequent during the period 2016-21. The quantity and quality of publicly available data from prospective clinical investigations across selected categories of cardiovascular devices, before and after CE approval during the period 2000-21, were deemed insufficient. The majority of studies was non-randomized, with increased risk of bias, and performed in small populations without provision of power calculations, and none of the reviewed devices had randomized trial results published prior to CE-mark certification.

Feasibility and efficacy of ultrasound-guided high-intensity focused ultrasound of breast fibroadenoma

Objective This nonrandomized prospective clinical trial aimed to assess the efficacy, safety and follow-up outcomes of ultrasound-guided high-intensity focused ultrasound (USgHIFU) surgery in patients with breast fibroadenoma. Methods With the approval of the institutional ethics committee and written informed consent, a total of 113 patients diagnosed with breast fibroadenoma by core-needle biopsy in our hospital were recruited. USgHIFU surgery was performed under local anesthesia. Contrast-enhanced ultrasound (CEUS) or contrast-enhanced MRI (CEMRI) was performed to evaluate the nonperfused volume (NPV). The patients were followed up with physical examination and ultrasound imaging. Results The clinical outcome of 85 patients with 147 fibroadenomas with a follow-up time of more than 3 months was analyzed in this study. Fifty-two patients had one lesion, twenty-one patients had two lesions and twelve patients had more than two lesions. During USgHIFU, the median localization time for all fibroadenomas was 3 (interquartile range: 1, 5) min, and the median treatment time was 9 (interquartile range: 5, 15) min. Under local anesthesia, all the patients tolerated the treatment well. No serious epidermal burns were observed in any of the patients. Based on CEUS or CEMRI imaging evaluation, the median NPV ratio was 100% (interquartile range: 79.2%, 116.8%). The VRR were 26.77 ± 50.05%, 50.22 ± 42.01% and 72.74 ± 35.39% at 3–6 months, 6–12 months and >12 months, respectively, which showed significant statistical difference (p < .001). Conclusion Ultrasound-guided HIFU surgery is an effective and safe noninvasive alternative technique for the treatment of breast fibroadenoma.

Comparing clinical outcomes between patients receiving non-absorbable and delayed absorbable sutures for abdominal wound closure after laparotomy

Background: There is a lot of debate about the best suture for repairing the abdominal fascia post-laparotomy. This research compared the clinical results of patients who received non-absorbable versus delayed absorbable sutures for abdominal wound closure after laparotomy. Methods: We conducted a prospective non-randomized clinical trial in the Department of General Surgery, Janaki Medical College and Teaching Hospital, Janakpur, Nepal. We included patients aged more than 18 years who underwent an elective laparotomy surgery with midline vertical incision for any indication between April 2020 till March 2022 in our department. Two study groups were formed: non-absorbable suture (polypropylene suture) and delayed absorbable suture (polydiaxanone suture). Results: The two study groups were similar with respect to indication of surgery (p value = 0.52). Bowel was opened in 81% in non-absorbable group and in 85% in delayed absorbable suture group. Mean duration of surgery was found to be significantly lower in the delayed absorbable suture group as compared to non-absorbable suture group (185±21.8 vs. 232±27.3 minutes, p value &lt; 0.05). Post-operative complications included surgical site infection, burst abdomen, incisional hernia and sinus formation. It was observed that surgical site infection rate was significantly higher among non-absorbable suture group patients as compared to delayed absorbable suture group (25% vs. 13%, p value &lt;0.05). Conclusions: Comparing early and late post-operative complications, there was no statistically significant difference between non-absorbable suture group and delayed absorbable suture group.