Non-randomized Pilot Study Research Articles

Relationship Between the Gut Microbiome, Tryptophan-Derived Metabolites, and Osteoarthritis-Related Pain: A Systematic Review with Meta-Analysis

Introduction: Osteoarthritis (OA) is the most prevalent form of arthritis and affects over 528 million people worldwide. Degenerative joint disease involves cartilage degradation, subchondral bone remodeling, and synovial inflammation, leading to chronic pain, stiffness, and impaired joint function. Initially regarded as a “wear and tear” condition associated with aging and mechanical stress, OA is now recognized as a multifaceted disease influenced by systemic factors such as metabolic syndrome, obesity, and chronic low-grade inflammation. Recent studies have focused on the gut-joint axis to investigate how the gut microbiome modulates inflammation and pain in OA. Materials and Methods: A systematic review was conducted following the PRISMA guidelines and was registered with PROSPERO (CRD42024556265). This review included studies involving adults with symptomatic OA and analyzed the relationship between the gut microbiome and OA-related pain. Randomized and non-randomized clinical trials, case reports, editorials, and pilot studies were excluded. Searches were performed in PubMed, Cochrane Library, and Web of Science without publication date restrictions, and filtered for “observational studies”. The study selection and data extraction were performed by two independent researchers, and the risk of bias was assessed using appropriate tools. Results: Five observational studies were included in the systematic review, and three were included in the meta-analysis. Two studies reported an association between different tryptophan metabolites and pain levels in patients with OA. Two other studies demonstrated a correlation between lipopolysaccharide levels and pain in OA. A fifth study confirmed the relationship between Streptococcus relative abundance of Streptococcus spp. and knee pain. These results were not supported by a meta-analysis, which found no significant association between the presence of pain in OA and the presence of bacilli of the genus Streptococcus or plasma markers of the tryptophan pathway. Conclusions: Current evidence indicates a potential link between gut microbiome dysbiosis and OA-related pain. However, methodological limitations preclude definitive conclusions. Further research using advanced techniques and larger cohorts is needed to validate and extend these findings and elucidate the underlying mechanisms. Targeted manipulation of the gut microbiome may be a valuable strategy for pain management in OA patients.

Safety of Adjunctive Intraarterial Tenecteplase Following Mechanical Thrombectomy: The ALLY Pilot Trial.

Recent studies suggest that the use of adjunctive intraarterial alteplase after mechanical thrombectomy (MT) may improve outcomes; however, there are limited data on the use of intraarterial tenecteplase, a newer-generation lytic, in this acute ischemic stroke patient population. Here, we evaluate the use of intraarterial tenecteplase in the ALLY pilot study (Adjunctive Intraarterial Tenecteplase Following Mechanical Thrombectomy). ALLY was a prospective, single-center, nonrandomized pilot study assessing the feasibility and safety of intraarterial tenecteplase up to 4.5 mg in acute ischemic stroke-large vessel occlusion MT patients with incomplete recanalization. The primary safety end point was any intracranial hemorrhage and neurological worsening by ≥4 points on the National Institutes of Health Stroke Scale within 24 hours of treatment with intraarterial tenecteplase. A post hoc analysis was performed with a control cohort of MT patients (ALLY MT) not receiving intraarterial tenecteplase. From April 2022 to July 2023, 218 MTs were performed at ProMedica Hospital (Toledo, OH), of which 20 patients were enrolled in ALLY. The mean age was 66.1±13.8 years, with 35% women. Median baseline National Institutes of Health Stroke Scale scores and Alberta Stroke Program Early CT Scores were 13 (interquartile range, 9-18.8) and 10 (interquartile range, 9-10), respectively. IV thrombolysis was administered in 55%. Most patients presented with middle cerebral artery occlusion (90%). Post-MT modified Treatment in Cerebral Ischemia grade was 2b and 2c in 11 and 9 patients, respectively. Final modified Treatment in Cerebral Ischemia 2b, 2c, and 3 was achieved in 55% (11/20), 35% (7/20), and 10% (2/20), respectively. Any intracranial hemorrhage was observed in 11 patients; however, only 1 patient had symptomatic intracranial hemorrhage. A favorable functional outcome (modified Rankin Scale score, 0-2) at 90 days was achieved in 50%. No difference in intracranial hemorrhage rates was observed between the ALLY and ALLY MT cohorts. The use of adjunctive intraarterial tenecteplase up to 4.5 mg in patients with acute ischemic stroke with incomplete reperfusion post-MT is feasible and was not associated with increased rates of hemorrhage. Larger, randomized studies are needed to assess the safety and efficacy of intraarterial tenecteplase in this population. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05172934.

Cost-Effectiveness Analysis of Family-Based Treatment With Additional Home Treatment for Adolescent Anorexia Nervosa.

Family-based treatment (FBT) is promising for treating adolescents with anorexia nervosa, but long-term remission rates are modest. Home treatment (HT) as a supplement to FBT aims to enhance sustainability and effectiveness by supporting recovery within the family. This study compares the cost-effectiveness of FBT alone versus FBT with additional HT for adolescents with anorexia nervosa. This cost-effectiveness analysis is based on a non-randomized pilot study, which examined the effectiveness of HT for adolescents with anorexia nervosa, disregarding the financial aspects. HT involved therapeutic interventions delivered in the patient's home environment, while FBT involved structured therapy sessions at the psychiatric clinic. Data from 61 patients were analysed, with 40 receiving FBT+HT and 21 receiving FBT only. Costs included FBT sessions, HT sessions, and inpatient treatment. Effectiveness was measured by weight restoration at thresholds of expected body weight (EBW)>85% and EBW>95%. FBT+HT promoted greater weight restoration within three months compared to FBT alone (70% vs. 52% at EBW>85%; 38% vs. 29% at EBW>95%). FBT+HT was more cost-effective, with lower average costs per patient meeting weight restoration criteria (8243 vs. 20,446 Swiss francs at EBW>85%; 15,387 vs. 37,485 Swiss francs at EBW>95%). Inpatient treatment accounted for most of the cost, with FBT+HT reducing hospitalisation needs. FBT with additional HT is a more cost-effective treatment for adolescents with anorexia nervosa. Although the cost-effectiveness index was relatively high, effective treatment could reduce the long-term burdens of this disorder. Larger long-term studies are needed to validate these findings and assess sustained cost-effectiveness.

Immediate effects of Vojta Therapy on gait ability in down syndrome patients: a pilot study

BackgroundVojta Therapy (VT) is a neurorehabilitation approach that targets ontogenetic postural function and automatic body posture control. Research has shown its potential to enhance gait ability. However, limited evidence exists regarding its immediate effects on individuals with Down syndrome (DS).ObjectivesThis study aimed to assess the immediate effects of one session VT on spatiotemporal gait parameters in individuals with DS.DesignA non-randomized pilot study was conducted.MethodsSixteen individuals with DS (mean age: 17.88 ± 4.57 years, 8 males) participated in this study. Each received a single VT session administered by an experienced physiotherapist. Spatiotemporal gait parameters before and after VT were analyzed using the Vicon motion capture system.ResultsSignificant improvements were observed in walking speed (m/s), cadence (steps/min), right step time (s), step length (cm), stride length (cm), and double support time (%GC) following the VT session (P < 0.05). These findings suggest that VT may offer immediate benefits in improving gait parameters for individuals with DS.ConclusionsFuture large-scale studies with more robust designs are necessary to explore the long-term effects of extended VT programs.

FoRSHE-X digital health intervention to improve the quality of life during chemotherapy among gynecological cancer survivors in Indonesia: A protocol for a pilot and feasibility study.

Most Indonesian gynecological cancer survivors have unmet supportive care needs during chemotherapy, which may lower their quality of life and discontinue the treatment. Digital health intervention can address this issue. This pilot investigation aims to (1) examine the feasibility and acceptability of a Fighting on distRess, Self-efficacy, Health Effects, and seXual issues (FoRSHE-X) intervention and (2) evaluate prospectively the impact of the study implementation on the level of distress, self-efficacy, side effects' knowledge and management, and sexual quality of life using the RE-AIM (Reach Effectiveness, Adoption, Implementation, and Maintenance) framework. This is a non-randomized mixed-methods pilot study. We will recruit women diagnosed with gynecological cancer undergoing chemotherapy to participate in the FoRSHE-X intervention consisting of ten weeks of social media-based education and telecoaching. We will evaluate the primary outcomes of study feasibility and acceptability, and the secondary outcomes of study impacts at three time points with quantitative and qualitative inquiries. We anticipate a minimum of 30 participants to enroll in the study and complete the assessment. We will disseminate results through conferences and peer-reviewed scientific journals. This study will imply whether a definitive trial to evaluate the potential benefits of the FoRSHE-X is viable and how it should proceed. The protocol can aid researchers or nurses in implementing this approach in their study or practice. Trial registration: Clinical trial registration number: ISRCTN13311651.

Innovations in Practice: Brief behavioral parent training for children with impairing ADHD characteristics - a pilot study.

Behavioral parent training (BPT) is a well-established intervention for children with attention-deficit/hyperactivity disorder (ADHD), but most programs are long, which may limit their accessibility. This could be improved by making programs shorter. Here, we studied (1) the feasibility of a new brief BPT program and its procedures, and (2) pre-post changes in daily rated problem behaviors (primary outcome), children's disruptive behaviors, ADHD/ODD characteristics, impairment, and parents' sense of parenting competence (secondary outcomes). We conducted a nonrandomized pilot study including parents of 28 children (4-12 years) with impaired ADHD characteristics. We examined treatment dropout, parent and therapist satisfaction, recruitment rates, study drop-out, measurement response and completion rates, acceptability of measurements according to parents, and treatment fidelity. Pre-post changes in the treatment group were compared to those in a historical control group using mixed model analysis, except for those outcomes that were not assessed in the control group. Within-group differences were analyzed for all outcomes. Feasibility of the program and study procedures were good. Treatment dropout was 14.2%, parents and therapists were satisfied with the new program. We recruited 1.5 participants per month, study dropout was 10.7%, response/completion rates ranged from 82% to 100%, measurements were acceptable for parents, and treatment fidelity was 96%. We found substantial within-group changes (d's = .68-.77) and medium-sized between-group changes (d's = .46-.48) on daily rated problem behaviors. We observed no changes on most of the secondary outcomes, except for disruptive behaviors and impairment. Our newly developed brief BPT program was feasible and we observed improvements in children's daily-rated problem behaviors. These results suggest that brief BPT might be beneficial for clinical practice if the findings are confirmed in large-scale randomized controlled trials.

A prospective study of the method of intraoperative luminescent spectroscopy in the application of isolated profundoplasty in hybrid surgery of critical ischemia of the lower limb

Introduction. Currently, it is relevant to develop new diagnostic criteria for assessing the condition of the deep femoral artery (DFA), in order to determine the possibilities of its use in various hybrid reconstructions for critical lower limb ischemia.Aim: To determine the indications for isolated profundoplasty as the final stage of proximal hybrid reconstruction using the method of intraoperative luminescence spectroscopy.Material and Methods. The prospective open-label non-randomized pilot study included 64 people operated at City Clinical Hospital No. 29 with a clinical diagnosis of “Obliterating atherosclerosis of the arteries of the lower extremities. Stenosis of the external iliac artery. Steno-occlusive lesion of the common femoral/superficial femoral artery. Stenosis of the deep femoral artery of the thigh. Chronic arterial ischemia of the III st.”, in the volume of proximal hybrid reconstruction, including isolated profundoplasty. The first group (n = 28) consisted of patients who had stenosis or occlusion of the mouth of the deep femoral artery, the second group (n = 20) – had diffuse lesion of the deep femoral artery, the third group (n = 16) – had a distal type of lesion of this artery. The first stage of the hybrid operation was stenting of the external iliac artery. The choice of further intraoperative tactics occurred as a result of an assessment of the anatomy and severity of the lesion of the deep femoral artery, by measuring the ankle-shoulder and hip-popliteal indices. All patients underwent intravascular luminescent spectroscopy intraoperatively using our technique to determine the luminescent compensation coefficient (CI). The follow-up period was 3 months. The end point of the study was thrombosis of the reconstruction zone. The SPSS 17.0 software was used for statistical data processing when comparing study groups.Results. When comparing the obtained CI, a direct strong correlation was noted with a preoperatively determined hip-popliteal index (r = 0.76; at p < 0.005). When assessing the interval of the hip-popliteal index from 0.3 to 0.4; 4 patients with thrombotic complications in the early postoperative period and 3 patients with no thrombotic complications were evaluated. When correlating CI in these categories of respondents, the statistically significant differences in indicators were established: CI (without complications) = 0.46 (0.43; 0.50); CI (complicated) = 0.59 (0.58; 0.60); with p < 0.05. When studying preoperative deep femoropopliteal index in representatives of study groups 1 and 2 who had GPI in the range from 0.4 to 0.5, but differed in the outcomes of the late postoperative period, the statistical significance of differences in indicators was noted: Cl (without complications) = 0.44 (0.43; 0.46); Cl (complicated) = 0.61 (0.60; 0.62); at p < 0.05.Conclusion. Intravascular luminescence spectroscopy is an important method of clarifying the intraoperative feasibility of performing isolated profundoplasty in addition to preoperative assessment of the degree of the hip-popliteal index.

Eccentric Resistance Exercise Effects on Older Adults With Metabolic Syndrome

Background This nonrandomized pilot study explored how whole-body eccentric resistance exercise training (ECC-RT) would change physical fitness and health parameters of older adults with metabolic syndrome symptoms. We hypothesized that ECC-RT would effectively improve neuromuscular and cardio-metabolic parameters. Methods Six men and 11 women aged between 62 and 79 (70.0 ± 5.0) years with body mass index >25 kg · m−2, dyslipidemia, and some indications of metabolic syndrome participated in this study. All performed 8 ECC-RT exercises of the major muscle groups twice a week for 8 weeks with a gradual increase in intensity from 10% to 100% of their maximal concentric strength assessed by 1-repetition maximum (1-RM) for each exercise. Before and after the training intervention, 1-RM strength of all exercises, physical function tests, sensory organization test (SOT) for balance, body composition, and some cardio-metabolic blood markers were measured. Results All participants completed 16 training sessions without any injuries or adverse effects. The concentric 1-RM strength increased (P < 0.05) for all exercises from baseline by 34.1% ± 13.8% (lateral pulldown) to 115.8% ± 108.7% (calf raise). Significant (P < 0.05) improvement of 400-m walk (12.8% ± 6.7%), repeated chair rise (18.6% ± 16.4%), timed up and go (13.6% ± 6.0%), and vestibular (26.1% ± 37.9%) and total score (6.5% ± 8.3%) in SOT were evident, although large variations in responses were observed among participants. However, no significant changes in body composition and blood markers were found. Conclusion The ECC-RT was tolerable for all participants and was effective for improving muscle strength and some physical function tests, but did not affect the metabolic syndrome parameters, possibly because of the short intervention period and small sample size.

Management of obesity with semaglutide or metformin in patients with antipsychotic-induced weight gain (MOSA): a non-randomised open-label pilot study

BackgroundAntipsychotic-induced weight gain (AIWG) represents a significant clinical challenge for both patients and clinicians, requiring appropriate interventions to prevent or reverse weight gain in patients using antipsychotics. Glucagon-like peptide 1 (GLP-1) agonists represent a novel approach to the management of obesity that has recently attracted considerable attention. Semaglutide (a GLP-1 agonist) has been demonstrated to result in notable weight loss. The present study investigates whether semaglutide is equally effective in achieving weight loss in patients with AIWG.MethodsA prospective, non-randomised cohort study was conducted with the objective of evaluating the efficacy and safety of oral semaglutide for the treatment of AIWG in routine outpatient clinical practice. Subsequently, the results were compared with those of a control group of AIWG patients taking metformin.ResultsAfter 16 weeks, the mean body weight loss was 4.5 kg (95% confidence interval (CI), -6.7 to -2.3 kg; p < 0.001) in the semaglutide group (n = 10) versus 2.9 kg (95% CI, -4.5 to -1.4 kg; p < 0.001) in the metformin group (n = 26). This corresponds to an average body weight loss of 4% for semaglutide, and 2.5% for metformin. The respective reductions in body mass index (BMI) and waist circumference were -1.7 kg/m2 (95% CI, -2.4 to -1.0 kg/m2; p < 0.001) and -6.8 cm (95% CI, -9.7 to -3.8 cm; p < 0.001) for semaglutide. The observed reductions for metformin were -0.8 kg/m2 (95% CI, -1.4 to -0.3 kg/m2; p = 0.001) and -3.4 cm (95% CI, -5.4 to -1.3 cm; p = 0.001). The differences between the two groups were not statistically significant. In both groups, adverse effects were typically mild and transient, predominantly nausea. Furthermore, psychiatric symptoms were reduced, and quality of life improved.ConclusionsOral semaglutide represents a viable, effective, and safe treatment option for psychiatric patients. However, further investigation is required to corroborate these findings.

Self-Cross-Linked Hyaluronic Acid Gel for Adhesion Prophylaxis in Laparoscopic Deep Endometriosis Removal: Safety Report of a Prospective Pilot Study

Background/Objectives: Surgical removal of deep endometriosis lesions is an established method of reducing patient symptoms, but it often results in iatrogenic adhesions that lead to further problems. This pilot study presents the safety evaluation of a novel self-cross-linked hyaluronic acid gel used to reduce adhesions after non-bowel deep endometriosis surgery. Methods: A single cohort, single-center, non-randomized pilot study was conducted in patients diagnosed with non-bowel deep endometriosis who underwent a three-stage treatment regimen consisting of first surgery, hormone therapy and second surgery. The present report is limited to an analysis of the inflammatory parameters, pain and complications occurring within a 72 h period following the initial laparoscopy (FLL) utilizing the anti-adhesion gel. Results: 60 patients (28.48 ± 5.9 years old) were included. 24 h after the intervention, a slight elevation in C-reactive protein levels was observed in 38.33% of cases (0.98 ± 1.46 mg/dL), with a statistically significant difference after FLL (0.98 ± 1.46 mg/dL before FLL vs. 1.03 ± 1.29 mg/dL after FLL; p =&lt; 0.001); there were no patients with levels above 10 mg/dL before or after surgery. 24 h after FLL, 29.33% of patients had a leukocyte count greater than 11 Thous/μL, with a maximum observed value of 16.2 Thous/μL. The count was found to be statistically significantly higher after FLL (6.03 ± 1.91 Thous/μL before FLL vs. 9.15 ± 2.61 Thous/μL after FLL; p =&lt; 0.001). At 72 h post-intervention, postoperative pain was reported in up to 63.33% of cases, and one urinary tract infection with fever occurred but was not considered to be related to the product. No serious adverse events were observed. Conclusions: The results of this exploratory study showed a safe range of inflammatory response within a 24 h period following the application of the novel self-cross-linked hyaluronic acid antiadhesion gel (HyaRegen®) in patients who underwent laparoscopic surgery for non-bowel deep endometriosis.

Fostering social-emotional competencies to improve social functioning, social inclusion, and school well-being: Results of a cluster non-randomized pilot study

BackgroundThe development of social competencies is key for enhancing both cognitive and non-cognitive skills among students. These competencies are central to students' ability to function socially, feel included, and experience overall well-being within the school environment. Schools can play an active role in promoting and shaping these outcomes by implementing various strategies. This study presents and reports on the outcomes of a six-week social-emotional intervention program implemented by class teachers. MethodsThe pilot study employed a two-arm cluster non-randomized trial with a pretest-post-test design. The study evaluates students' social competencies as the primary outcome and social functioning, social inclusion, and school well-being as the secondary outcomes. Students in the intervention group participated in a six-week social-emotional learning intervention, attending two sessions each week, while the control classes followed the regular curriculum. ResultsData were collected from both teachers and students. Student-reported data were collected from 266 students (n = 124 girls, n = 142 boys) aged 8 to 14 (M = 9.84) and from teachers on 212 students (n = 92 girls; n = 115 boys). Results of the linear mixed model analysis showed for teacher reporting on students’ outcomes a decrease in internalizing (β = -0.85, p = 0.035) and externalizing behavior problems for students in intervention classes (β = -6.84, p = 0.020). No significant changes were observed in social-emotional competencies, social inclusion and school well-being. ConclusionAfter the social-emotional intervention program reduced internalizing and externalizing behavior problems were observed, with age moderating both outcomes. The results are consistent with previous research; however, they also suggest that the intervention could benefit from adjustments, such as a longer implementation period and follow-up evaluation. External factors such as the COVID-19 pandemic and repeated school closures at the time of the study may have impacted the results additionally.

A Nonrandomized Pilot Study to Investigate the Acceptability and Feasibility of LivR Well: A Multifaceted 28-Day Home-Based Liver Optimization Program for Acute-on-Chronic Liver Failure

Background and AimsAcute-on-chronic liver failure (ACLF) has a 22-74% 28-day mortality rate and 30-40% 30-day re-admission rate. We investigated the acceptability and feasibility of a multimodal community intervention for ACLF. MethodsA single-arm, non-randomized pilot study of consecutive participants with ACLF was conducted in a tertiary health service. Participants received weekly medical and nursing reviews, dietetics, physiotherapy, pharmacy, social work, addiction medicine, and/or neuropsychiatry. A digital platform included remote weight monitoring, and online surveys. The primary outcome was acceptability/feasibility. Secondary outcomes included safety, mortality, re-admission, liver disease severity, and costs. ResultsFifty-nine patients were enrolled with median age 51 years (IQR: 45-59); majority alcohol etiology (74%),and median Model for End-Stage Liver Disease Sodium (MELD-Na) score 16 (IQR: 12-21). LivR Well was acceptable with low attrition (8/59), adherence to the program including home visits (mean 8.4±4.2) and consultations (mean 2.4±1.5) per patient. This was supported by positive feedback and themes identified through a qualitative sub-analysis. Feasibility was demonstrated by recruitment rate of 4.94 patients/month and 86% completion. Mortality was lower than expected at 3%, 30-day readmission rate was 15%, and median MELD-Na score reduced to 15 (p = 0.01). Median 6-month costs reduced from $30,454 (IQR: 21953-$65657) to $17, 657 ($4249-42876) (p=0.009). The total 6-month healthcare cost was $1,868,859 (95% CI 1,081,821-2,655,897) compared to $2,518,227 (95% CI 1,959,610-3,076,844). ConclusionLivR Well was acceptable, feasible and safe with low short-term mortality and readmission rates. Healthcare costs were reduced by 26% driven by a 40% reduction in 30-day re-admission. Further evaluation includes a randomized, controlled trial of LivR Well compared to standard care.

Supporting primary care practitioners to promote dementia risk reduction in Australian general practice: outcomes of a cross-sectional, non-randomised implementation pilot study.

Background Primary care practitioners worldwide are urged to promote dementia risk reduction as part of preventive care. To facilitate this in Australian primary care, we developed the Umbrella intervention, comprising a waiting room survey and patient information cards for use in consultations. Educational and relational strategies were employed to mitigate implementation barriers. Methods In this cross-sectional, non-randomised implementation study within the South East Melbourne Primary Health Network, we employed mixed-methods outcome evaluation. Antecedent outcomes (acceptability, appropriateness, and feasibility) and actual outcomes (adoption, penetration, and fidelity) were assessed from the perspective of primary care practitioners and patients. Results Five practices piloted the intervention and implementation strategies, including 16 primary care practitioners engaging with 159 patients. The Umbrella intervention was deemed acceptable, appropriate, and feasible, but penetration was limited. Approximately half of eligible primary care practitioners used the intervention, with moderate fidelity. Engagement with implementation strategies was similarly limited. While most strategies were well-received, improvements in online peer discussions and staff readiness were desired. Conclusions The Umbrella intervention is a viable approach to promoting dementia risk reduction in Australian general practice, supported by educational and relational strategies. Stakeholder-informed refinements to enhance uptake are recommended before advancing to a definitive trial.

Internet-based cognitive behavioral therapy for individuals with gambling disorder in Indonesia: protocol for a pilot and feasibility study.

Gambling disorder (GD) has become a wide concern in Indonesia, as many negative consequences arise from this psychiatric condition. Prompt treatment with an appropriate method of delivery is required to achieve optimal outcomes in GD patients. This protocol paper outlines a study to determine the effectiveness, acceptability, and feasibility of internet-based cognitive behavioral therapy (iCBT) in treating GD in Indonesia. This non-randomized pilot and feasibility study will recruit 20 people with GD. All participants will receive the iCBT intervention through self-learning videos and guided weekly group sessions. The effectiveness of the intervention will be assessed at baseline (week 0), post- treatment completion (week 10), and 6 weeks post-treatment (week 16). The outcomes measured will be the change in gambling symptoms, gambling urges, cognitive distortions, readiness to change, emotional problems, and quality of life of the participants. The feasibility of iCBT for GD patients in Indonesia will be assessed by this study. The study's results will give an indication of the acceptability of the intervention and the feasibility of a subsequent conclusive trial. The delivery of iCBT may help to address the issue of treatment access in an extensive geographical region and provide immediate implications as a treatment resource for GD in practice.

Erosion regression in patients with rheumatoid arthritis after upadacitinib-a pilot study using high resolution peripheral quantitative computed tomography.

To evaluate whether inhibition of Janus kinases (JAK) 1 could lead to erosion repair on high-resolution peripheral quantitative computer tomography (HR-pQCT) in patients with active rheumatoid arthritis (RA). This was a prospective, non-randomized pilot study. We enrolled 20 adult patients with active RA with ≥1 bone erosion on HR-pQCT. They were given upadacitinib 15 mg once daily for 24 weeks. HR-pQCT of the metacarpophalangeal joint was performed at baseline and 24-week. The serum bone biomarkers level was evaluated before and after treatment. Twenty age-and-sex matched RA patients from another study treated with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) were included as active controls. Nineteen patients in the upadacitinib group completed the study procedures. After 24 weeks, despite similar improvement in disease activity, a reversed trend in the mean erosion volume change on HR-pQCT was observed comparing the upadacitinib and active control group (upadacitinib group: -0.23 ± 3.26mm3 vs control group: 1.32 ± 6.05mm3, p= 0.131). A greater proportion of erosions in the upadacitinib group demonstrated regression (27% vs 12%, p= 0.085). Using general estimating equation (GEE), the use of upadacitinib was significantly associated with erosion regression (OR: 3.61, 95% CI: 1.00-13.00, p= 0.049) after adjusting for the difference in disease duration. The serum levels of bone resorption markers reduced after upadacitinib treatment. No new safety signal was noted. Despite a similar improvement in RA disease activity after upadacitinib compared with csDMARDs, a differential regression of erosion on HR-pQCT was observed in patients received upadacitinib. The potential role of JAK1 inhibition in erosion repair should be investigated.

Intravenous Lidocaine for Refractory Pain in Patients With Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis: A Multicenter Prospective Nonrandomized Pilot Study.

Refractory pain is a major clinical problem in patients with pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). New, effective therapies to reduce pain are urgently needed. Intravenous lidocaine is used in clinical practice in patients with PDAC and CP, but its efficacy has not been studied prospectively. Multicenter prospective nonrandomized pilot study included patients with moderate or severe pain (Numeric Rating Scale ≥ 4) associated with PDAC or CP in 5 Dutch centers. An intravenous lidocaine bolus of 1.5 mg/kg was followed by continuous infusion at 1.5 mg/kg/hr. The dose was raised every 15 minutes until treatment response (up to a maximum 2 mg/kg/hr) and consecutively administered for 2 hours. Primary outcome was the mean difference in pain severity, preinfusion, and the first day after (Brief Pain Inventory [BPI] scale 1-10). A BPI decrease ≥1.3 points was considered clinically relevant. Overall, 30 patients were included, 19 with PDAC (63%) and 11 with CP (37%). The mean difference in BPI at day 1 was 1.1 (SD ± 1.3) points for patients with PDAC and 0.5 (SD ± 1.7) for patients with CP. A clinically relevant decrease in BPI on day 1 was reported in 9 of 29 patients (31%), and this response lasted up to 1 month. No serious complications were reported, and only 3 minor complications (vertigo, nausea, and tingling of mouth). Treatment with lidocaine did not impact quality of life. Intravenous lidocaine in patients with painful PDAC and CP did not show an overall clinically relevant reduction of pain. However, this pilot study shows that the treatment is feasible in this patient group and had a positive effect in a third of patients which lasted up to a month with only minor side effects. To prove or exclude the efficacy of intravenous lidocaine, the study should be performed in a study with a greater sample size and less heterogeneous patient group.

Comparing the effects of resistance and aerobic exercise on mood-related symptoms and EEG activity in young healthy adults: A non-randomized pilot study

Background and aimsExercise offers several benefits in combating mood-related symptoms in humans. Participation in various types of physical activity improves brain and mental health. However, the different effects and mechanisms depending on the type of exercise on an individual's mood and brain remain unclear. This pilot trial aimed to reveal the feasibility of the effects of resistance and aerobic exercise on mood-related symptoms and explain the different patterns of brain waves. MethodsThis 15-week single-arm pre-test/post-test trial including 3 measurement periods was held in Seoul, Republic of Korea. Overall, 18 healthy participants aged 19–29 years were recruited. After 6 weeks of respective aerobic and resistance exercise, anxiety/depression-related questionnaire scores and electroencephalography (EEG) changes were measured (single blinded outcome assessment). Specifically, changes in frontal alpha asymmetry (FAA), absolute band power of beta waves, and theta waves were measured in the prefrontal and frontal regions, which play a critical role in regulating mood and cognition. ResultsResistance exercise resulted in a significant reduction in Beck Depression Inventory-II scores (p = 0.002, effect size = 0.76) while significant improvement was shown in Beck Anxiety Inventory scores (p = 0.01, effect size = 0.77) after aerobic exercise. In regarding EEG analysis, ten participants completed the assessment. After resistance exercise, there was a significant elevation in frontal beta waves (p = 0.01, effect size = 0.81). Aerobic exercise did not result in significant EEG changes. There were no adverse events related to study participation. ConclusionOur findings suggest that resistance and aerobic exercises may be feasible for the alleviation of mood-related symptoms and EEG activities. As our pilot trial has a small sample size and did not include a control group, future research that accurately reflects the effects of different types of exercises on mood symptoms and changes of EEG activities is required.

Acute toxicities in proton therapy for head and neck cancer – A matched analysis of the DAHANCA 35 feasibility study

Background and purposeAs preparation for a national randomized study comparing proton radiotherapy to photon radiotherapy, DAHANCA 35, we performed a non-randomized pilot study to investigate patient selection, logistics, planning, and treatment delivery. With the present study, as a comprehensive safety analysis, we want to compare toxicity during and up to two months after therapy to a historically matched group of patients treated with photon radiotherapy. Materials and methods62 patients treated with protons were matched to 124 patients who received photon treatment outside a protocol. Available data were retrieved from the DAHANCA database. Patients were matched on treatment centre, concurrent chemotherapy, tumour site, stage, p16 status for oropharynx cancers. Selection of patients for proton therapy was based on comparative treatment plans with a NTCP reduction for dysphagia and xerostomia at six months. ResultsBaseline characteristics between groups were well balanced, except for the type of drug used concurrently; more photon patients received Carboplatin (21.2 % vs 5.8 %, p = 0.01). Proton therapy was associated with significantly less weight loss at the end of treatment, mean weight loss of 3 % for protons and 5 % for photons (p < 0.001). There were more grade 3 skin reactions and grade 3 mucositis after proton treatment compared with photons at the end of treatment, Risk Ratio (RR) 1.9 (95 % CI: 1.01–3.5, p = 0.04) and RR 1.5 (95 % CI: 1.3–1.7, p < 0.001), respectively. All differences resolved at follow up two months after treatment. There were no significant differences between groups on opioid use, use of feeding tubes, or hospitalization during the observation period. ConclusionProton treatment resulted in excess objective mucositis and dermatitis, which was transient and did not seem to negatively influence weight or treatment compliance and intensity. Selection bias was likely especially since NTCP models were used for selection of proton treatment and photon treated patients were matched manually. We are currently including patients in a randomized controlled trial.

In-person psychoeducational intervention to reduce rehospitalizations and improve the clinical course of major depressive disorder: a non-randomized pilot study.

Emerging issues in the management of major depressive disorder (MDD) comprise a nonadherence to treatment and treatment failures, depressive recurrence and relapses, misidentification of incoming exacerbated phases and consequently, a chronification of depression. While antidepressant drugs constitute the standard of care for MDD, effective psychosocial interventions are needed to reduce rehospitalizations and other adverse events. The present study primarily investigated the effects and impact of implementing a structured psychoeducational intervention on the clinical course of MDD. A non-randomized comparative, pragmatic, pilot, single-center study of adults with nonpsychotic moderate or severe episode of MDD recently discharged from a psychiatric hospitalization. The consecutive subjects were allocated either to the intervention group (N=49) or to the attention control group (N=47), based on their preference. The psychoeducational intervention was based on a modified Munoz's Depression Prevention Course. Subjects were followed up prospectively for two years. The absolute changes in Beck anxiety inventory scale, Zung's depression questionnaire, and Montgomery and Äsberg depression rating scale (MADRS) total scores at 6-month follow-up were comparable between the two groups. There were lower rates of the rehospitalization within one year (2.1% vs. 16.7%; P<0.001) and less rehospitalizations after one year (6.3% vs. 25%; P<0.001), lower rates of the ongoing sickness absence (11.5% vs. 29.2%; P<0.001), less persons with disability due to MDD at 1-year follow-up (1% vs. 11.5%; P=0.002), and less nonadherent subjects who self-discontinued treatment (6.3% vs. 28.1%; P<0.001) among participants in the intervention group compared to the control group. The disability due to MDD at 1-year follow-up was predicted by the absence of the psychoeducational intervention (P=0.002) and by the MADRS total score at 6-month follow-up (OR 1.10; 95% CI 1.003-1.195; P=0.044). Qualitative data indicated the intervention was desired and appreciated by the participants, as well as being practical to implement in Slovakian clinical settings. The results suggest the psychoeducational intervention based on a modified Munoz's Depression Prevention Course has beneficial effects in adults with MDD recently discharged from a psychiatric hospitalization. The findings implicate the psychoeducational intervention may offer a new approach to the prevention of depressive relapses.

P-795 Robust and simple in vitro maturation of ovarian tissue oocytes

Abstract Study question Using in-vitro gametogenesis results in mice, can we perform simple, robust in-vitro maturation (IVM) of oocytes from human ovarian tissue? Summary answer In vitro oogenesis in mice reveals 3 phases of oocyte maturation, IVD, IVG, and IVM. In vivo IVD and IVG simplifes a more robust IVM. What is known already For fertility preservation in cancer patients, IVM of GV’s obtained from ovary tissue with live birth has been achieved, but the results are variable, and great effort has gone into trying to make the “right” culture media, and most are given booster shots of gonadotropin with questionable results. It is easy to obtain many GV oocytes from tiny follicles using open cortical dissection. But it still has remained a puzzle how to do robust IVM in the best way. Study design, size, duration A total of 146 females underwent ovary tissue cryopreservation since 1977. The most recent 38 consecutive such patients between 2 and 38 years of age underwent in-vitro maturation of oocytes (IVM) derived from their ovarian tissue. This is a prospective non-randomized pilot study based upon our results with in vitro oogenesis. Participants/materials, setting, methods After ovarian cortex dissection, the spent media is examined for cumulous complexes (CC’s), which were placed in culture with widely varying concentrations of FSH and HCG, and in a variety of different media. Based on now established mechanisms of in vitro oogenesis, we postulated that the specific media for IVM and the concentrations of HCG would not impact results. There was no prior hormone administration. Main results and the role of chance The harvested germinal vesicle oocyte developed into mature metaphase II oocytes with simple culture media just as well as with “IVM media”, and with HCG concentration from 10 mIU/l to 1000 mIU/l. Of the 38 cases, 18 had had previous chemotherapy or were pre-pubertal. None of these had CC’s. Of the 20 who were post-pubertal and had not yet undergone chemotherapy, the number of CC’s averaged 20 per patient. Of a total of 402 GV oocytes, 137 became mature MII’s (34.1%), varying between 20% and 56%. The only case with low maturation rate (9%) occurred when the cumulus was stripped immediately instead of at 24 hours. Thus mature oocytes can robustly and easily be obtained from ovary tissue with simple media and no need for ovarian stimulation. Furthermore, ovarian stimulation and ovulation are not necessary for oocyte maturation. Oocytes that have just exited IVD that have been exposed to less than 7 days of gonadotropin (IVG) will not mature. Those oocytes exposed to more than 11 days of IVG will degenerate. Thus about 35% of oocytes at any given time will have already been properly prepared in vivo for IVM. Limitations, reasons for caution This is an early proof of concept study in humans with only 30 participants. However, it is completely consistent with what we have predicted from in vitro oogenesis in the mouse. Wider implications of the findings Ovary tissue freezing along with robust IVM will at once provide cancer patients with two possibilities for fertility preservation, without having to delay cancer treatment. Four months of in vivo IVD (non-hormonal) followed by 11 days of IVG (FSH) have already prepared oocytes for IVM. Trial registration number not applicable