Prospective Randomized Multicenter Study Research Articles

Effectiveness of neck-specific exercises with and without internet-based support on dizziness/unsteadiness in chronic whiplash-associated disorders: Secondary analyses of a randomised controlled trial.

To investigate the effectiveness in individuals with chronic whiplash-associated disorders (WADs) of neck-specific exercise (NSE) supervised by a physiotherapist twice a week for 12 weeks versus neck-specific exercise with internet support and four physiotherapy visits (NSEIT) regarding dizziness, unsteadiness and balance, and to investigate the differences between WAD grades. This is a secondary analysis of a prospective randomised multicentre study (RCT) with concealed allocation (ClinicalTrials.gov Protocol ID: NCT03022812). The outcomes were dizziness measured on the Dizziness Handicap Inventory (DHI); dizziness at rest and during activity and unsteadiness using visual analogue scales; and standing on one leg with eyes closed (SOLEC). Participants (n = 140) were randomised to NSE or NSEIT. Measurements were obtained at baseline, and at three- and 15-month follow-ups by assessor-blinded investigators. There were no significant differences between NSEIT and NSE in any of the outcomes (p>0.38). Both NSEIT and NSE improved over time (p<0.02; effect size (ES) = 0.74-1.01) in DHI score and dizziness during activity. There was a significant group-by-time interaction effect in dizziness (at rest: p = 0.035; ES: 0.66; and during activity: p = 0.016; ES: 1.24) between WAD grades. Individuals with WAD grade 3 had dizziness/unsteadiness to a greater extent and improved in all outcomes over time (p<0.04) compared to those with WAD grade 2, except for SOLEC. There were no significant group differences between NSEIT and NSE. Both groups decreased in terms of self-reported dizziness (DHI, dizziness during activity), with medium to large effect size. Those with WAD grade 3 have dizziness/unsteadiness to a greater extent than those with WAD grade 2. Despite improvements, many participants still reported dizziness at 15-month follow-up, and additional balance training and/or vestibular exercise may be investigated for potential additional effect.

Ultrathin semirigid retrograde ureteroscopy versus antegrade flexible ureteroscopy in treating proximal ureteric stones 1-2cm, a prospective randomized multicenter study.

To compare the outcomes of using Ultrathin semirigid retrograde ureteroscopy and antegrade flexible ureteroscopy to treat proximal ureteric stones of sizes 1-2cm. A prospective randomized multicenter study included patients who had proximal ureteric stones 1-2cm, amenable for ureteroscopy and laser lithotripsy between August 2023 and February 2024. Two hundred thirty patients were divided evenly into two treatment groups. Group I included patients treated with antegrade flexible ureteroscopy and holmium laser stone fragmentation, and Group II included patients treated with retrograde ultrathin semirigid ureteroscopy. The study groups were compared in terms of patient demographics, stone access success, operation time, reoperation rates, peri-operative complications, and stone-free status. Group I included 114 patients, while Group II included 111. The mean age of the patients was 33.92 ± 10.37years, and the size of the stones was 15.88 ± 3mm. The study groups had comparable demographics and stone characteristics. The mean operative time was significantly longer in group I than in group II (102.55 ± 72.46min vs. 60.98 ± 14.84min, respectively, P < 0.001). Most reported complications were MCCS grades I and II, with no significant difference between the study groups. The stone-free rate after four weeks was 92.1% and 81.1% for groups I and II, respectively, which increased to 94.7% and 85.6% after eight weeks (P > 0.05). Antegrade flexible ureteroscopy is equivalent to retrograde ultrathin semirigid ureteroscopy in treating proximal ureteric stones regarding stone-free status and procedure-related morbidity. However, the antegrade approach has a longer operative time, greater fluoroscopy exposure, and longer hospital stays.

Results of a Prospective Randomized Multicenter Study Comparing Indocyanine Green (ICG) Fluorescence Combined with a Standard Tracer Versus ICG Alone for Sentinel Lymph Node Biopsy in Early Breast Cancer: The INFLUENCE Trial.

For clinically node-negative early breast cancer patients, sentinel lymph node biopsy (SLNB) using dual localization with blue dye and radioisotope (RI) is currently standard of care. Documented disadvantages with these tracers have prompted exploration of alternative agents such as fluorescent indocyanine green (ICG), which demonstrates high detection rates combined with other tracers. Results of a randomized study evaluating ICG as a single tracer for SLN identification are presented. Overall, 100 patients with unilateral, clinically node-negative, biopsy-proven invasive breast cancer (≤5cm) scheduled for SLNB were recruited in two separate randomized cohorts, with 50 patients receiving ICG alone. Cohort 1 received ICG alone (n=25) or combined with RI [Technetium99] (n=25), while Cohort 2 received ICG alone (n=25) or combined with blue dye (n=25). The primary outcome was sensitivity for SLN identification. Among evaluable patients (n=97), the overall SLN identification rate was 96.9% (ICG alone = 97.9%; ICG + RI = 100%; ICG + blue dye = 92%). Node positivity rates were 14.9% for ICG alone, 16% for ICG combined with RI, and 20% for ICG combined with blue dye. There were no significant differences (p<0.05) in performance parameters, with ICG alone being non-inferior to tracer combinations for procedural node positivity rates when adjusted for specific factors. These results support potential use of ICG as a sole tracer agent for routine SLNB, thereby avoiding disadvantages of RI and/or blue dye. The latter can be safely withheld as a co-tracer without compromising detection of positive nodes in primary surgical patients.

Haemodynamic effect of dexmedetomidine during paediatric kidney transplantation.

Dexmedetomidine is increasingly used for its ability to stabilise haemodynamic status during general anaesthesia. However, there is currently no data on paediatric kidney transplant recipients (pKTR). This study investigates the haemodynamic impact of dexmedetomidine administered perioperatively in pKTR. From 2019 to 2023, a retrospective study was conducted at Nantes University Hospital involving all pKTR under 18 years of age. The study compared intraoperative haemodynamic parameters between patients administered dexmedetomidine during kidney transplantation (DEX group) and those who did not receive it (no-DEX group). Mean arterial pressure (MAP) and heart rate (HR) were monitored throughout the duration of anaesthesia and compared. Graft function was assessed based on creatinine levels and glomerular filtration rate (GFR) at specific intervals. The perioperative use of fluids and vasoactive drugs, as well as their administration within 24 h post-surgery, were analysed. Thirty-eight patients were enrolled, 10 in the DEX group and 28 in the no-DEX group. Intraoperative HR was similar between the groups; however, MAP was higher in the DEX group (mean difference 9, standard deviation (SD, 1-11) mmHg, p = 0.039). No differences were found regarding the use of fluid and vasoactive drug therapy between groups. GFR at 1 month post-transplantation was significantly elevated in the DEX group (p = 0.009). pKTR receiving intraoperative dexmedetomidine exhibited higher perioperative MAP compared to those not administered dexmedetomidine. Additionally, the DEX group demonstrated superior graft function at 1 month. The direct impact of dexmedetomidine on immediate postoperative graft function in pTKR warrants further investigation in a prospective multicentre randomised study.

Prospective randomized multicenter study to evaluate holmium vs. new thulium fiber laser for prostate enucleation.

Benign prostatic hyperplasia (BPH) commonly causes lower urinary tract symptoms (LUTS) in men. Holmium (HoLEP) and thulium (ThuLEP) laser enucleation are established techniques for BPH treatment. Thulium fiber laser (TFL) for prostate enucleation (ThuFLEP) shows promising outcomes. A prospective randomized multicenter study was conducted. Patients with BPH and LUTS unresponsive to medical therapy were enrolled. Preoperative, surgical, perioperative and postoperative data were recorded with follow-up at 3 and 6 months. The primary outcome was functional improvement, and the secondary outcome was safety in terms of complications. Two hundred patients were included (HoLEP 100, ThuFLEP 100). No significant baseline difference was found between groups. At 3 and 6 months we found statistically significant improvements from baseline for both HoLEP and ThuFLEP in efficacy: International Prostatic Symptoms Score (IPSS), IPSS-Quality of Life (QoL), maximum urinary flow rate (Q<inf>max</inf>), and post-void residual volume (PVR; P<0.05). At 6 months, mean±SD IPSS, IPSS-QoL, Q<inf>max</inf>, and PVR for HoLEP vs. ThuFLEP were 5.8±4.9 vs. 4.8±5.0 points (P=0.57), 1.6±1.4 vs. 0.7±1.1 points (P=0.09), 29.9±12.5 vs. 29.6±8.0 mL/s (P=0.8), and 16.3±17.7 vs. 15.5±13.4 mL (P=0.92), respectively. No intraoperative complication was recorded. No Clavien-Dindo ≥III complications occurred during hospitalization. After 6 months, 8 (8%) and 6 (6%) patients reported mild stress urinary incontinence in HoLEP and ThuFLEP groups, respectively (P=0.24). Urethral stenosis was observed in 3 men (3%) in the HoLEP group and 1 subject (1%) in the ThuFLEP group (P=0.72). HoLEP and ThuFLEP are effective and safe for BPH treatment, with comparable functional outcomes and complication rates at 6 months. Further research is needed to confirm these findings.

Are Two Gliflozins Different: A Prospective Multicenter Randomized Study to Assess Effect of Remogliflozin Compared With Empagliflozin on Biomarkers of Heart Failure in Indian Patients With Type 2 Diabetes Mellitus with Chronic Heart Failure (REMIT-HF Study)

BackgroundThere is limited data comparing two gliflozins on their effect on biomarkers in diabetic patients with chronic heart failure. MethodsA prospective, multicenter, active controlled, double-arm, investigator-initiated, interventional study enrolled 250 adults with T2DM and comorbid CHF (LVEF<40%; NT-proBNP >600pg/ml). 125 patients were allocated each to Remogliflozin (R) and Empagliflozin (E) group and followed up for 24 weeks. The primary endpoint was the mean percentage change from baseline in NT-proBNP level after 24 weeks. ResultsThere was significant improvement from baseline in mean NT-proBNP level in both groups after 24 weeks however there was no significant difference between the two groups (p= 0.214). The mean NT-proBNP level improved from 2078.15±1764.70 pg/ml at baseline to 1185.06±1164.21 pg/ml at 6 months in R-group (p≤0.001) and from 2283.98±1759.15 pg/ml at baseline to 1395.33±1304.18 pg/ml at 6 months in E-group (p= <0.001). Left ventricular ejection fraction (LVEF) and LV volumes improved in both the groups. The glycemic parameters (HbA1c, FPG and PPG) demonstrated a significant reduction from baseline to week 24 in both groups. Similar improvement was seen in heart rate, blood pressure and weight reduction over 6 months in both groups. There was no drug related serious adverse event in any group. ConclusionRemogliflozin and Empagliflozin significantly improves glycemic parameters and NT-proBNP levels as the index of the therapeutic effects in T2DM patients with CHF. The positive effects are comparable in both groups.

A Prospective Randomized Multicenter Study on the Impact of [18F]F-Choline PET/CT Versus Conventional Imaging for Staging Intermediate- to High-Risk Prostate Cancer.

This study aimed to compare the efficacy of [18F]F-choline PET/CT with conventional imaging for staging and managing intermediate- to high-risk prostate cancer (PCa). The primary objective was to assess the ability of PET/CT with [18F]F-choline to identify lymph node and systemic involvement during initial staging. Secondary objectives included evaluating the impact of [18F]F-choline PET/CT on unnecessary local treatments and assessing the safety of [18F]F-choline agents. Additionally, the study aimed to analyze recurrence-free survival and overall survival 5 y after randomization. Methods: A prospective controlled, open, randomized multicenter phase III trial involving 7 Italian centers was conducted. Eligible patients with intermediate- to high-risk PCa were randomized in a 1:1 ratio. Two groups were formed: one undergoing conventional imaging (abdominopelvic contrast-enhanced CT and bone scanning) and the other receiving conventional imaging plus [18F]F-choline PET/CT. The study was terminated prematurely; however, all the endpoints were thoroughly analyzed and enriched. Results: Between February 2016 and December 2020, 256 patients were randomly assigned. In total, 236 patients (117 in the control arm and 119 in the experimental arm) were considered for the final assessment. In the experimental arm, the sensitivity for lymph node metastases, determined by final pathology and serial prostate-specific antigen evaluations, was higher than in the control arm (77.78% vs. 28.57% and 65.62% vs. 17.65%, respectively). The [18F]F-choline was tolerated well. The use of [18F]F-choline PET/CT resulted in an approximately 8% reduction in unnecessary extended lymphadenectomy compared with contrast-enhanced CT. Additionally, [18F]F-choline PET/CT had a marginal impact on 5-y overall survival, contributing to a 4% increase in survival rates. Conclusion: In the initial staging of PCa, [18F]F-choline PET/CT exhibited diagnostic performance superior to that of conventional imaging for detecting metastases. [18F]F-choline PET/CT reduced the rate of unnecessary extensive lymphadenectomy by up to 8%. These findings support the consideration of discontinuing conventional imaging for staging PCa.

Hand, foot, and mouth disease: could EPs® 7630 be a treatment option? A prospective randomized open-label multicenter clinical study.

Hand, foot and mouth disease (HFMD) is a viral contagious disease of children caused by human enteroviruses (EVs) and coxsackieviruses (CVs). There is no specific treatment option for HFMD. EPs® 7630's anti-infective and immunomodulatory properties have previously been demonstrated in several in vitro and in vivo studies; however, the use of this herbal medicine in children with HFMD has not previously been investigated. This prospective randomized multicenter clinical study included 208 children with HFMD. The diagnosis was made by pediatricians. The patients who were within the first 48 h of symptom onset (according to the first onset of fever and skin findings) were enrolled. The study participants were assigned into 2 groups as EPs® 7630 and control groups. All patients were followed up twice more, 48 h after the first admission and on the 5th-7th day. Another phone evaluation was conducted for those with continued complaints from the previous visit. The median age was 27 (12-112) months. The male-female ratio was 0.98. One hundred thirty one (63%) of 190 patients had no history of household contact. EPs® 7630 group included 94 and control group included 96 patients. A significant difference was found between the groups in terms of complaint scores at the visits made at the 48th h of the treatment and on days 5-7 (p < 0.001). The mean ± SD disease duration of EPs® 7630 users was significantly shorter 6.07 ± 0.70 days (95% CI: 5.92-6.21)] than the control group [8.58 ± 0.94 days (95% CI: 8.39-8.77)] (p < 0.001). Besides, the hospitalization rate among the EPs® 7630 users were significantly lower (p = 0.019). No side effects were observed, except for unpleasant taste, which was reported in 5 patients (EPs® 7630 group). Considering its efficacy and safety profile EPs® 7630 may represent a feasible herbal-based treatment option for children with HFMD. ClinicalTrials.gov, identifier (NCT06353477).

Abstract PO2-23-02: Results of a prospective randomised multicentre study comparing indocyanine green (ICG) fluorescence combined with a standard tracer versus ICG alone for sentinel lymph node biopsy in early breast cancer: The INFLUENCE Trial

Abstract Background: Use of fluorescence mapping for visualization of lymphatic and nodal tissue for sentinel lymph node biopsy (SNB) reveals high rates of identification (&amp;gt;98%). Studies combining ICG with either blue dye or radioisotope (RI) have shown high levels of concordance (&amp;gt;90%) and comparable performance parameters between ICG and standard tracers for SNB localization. ICG combines many advantages of blue dye and RI without the disadvantages of allergic reactions, staining of skin and surgical tissues along with handling and disposal of radioactivity materials. Moreover, magnetic tracers pose challenges of interference relating to surgical instrumentation and magnetic resonance imaging (MRI). The combination of ICG with a conventional tracer may represent a transition phase and this randomized study evaluates ICG as a sole tracer agent for SNB in early-stage breast cancer. Methods: In a prospective randomized study, 100 patients with unilateral clinically node negative tumours scheduled to undergo routine SNB for core-biopsy proven invasive breast cancer (≤5cm) were identified at multidisciplinary meetings [non-invasive tumours excluded]. All patients had pre-operative axillary ultrasound and breast conserving surgery or mastectomy. Patients were recruited in two cohorts (n=50); cohort 1 was assigned to either ICG [2ml 0.5%] alone (n=25) or combined with RI [Technetium99 nanocolloid, 20MBq] (n=25). Cohort 2 received ICG alone (n=25) or combined with blue dye for SNB localization. The number of nodes whether blue, radioactive, fluorescent or a combination thereof were recorded. Lymphatic and nodal tissue was visualized with a fluorescent camera/detection system. Sensitivity of ICG alone and/or in combination with one or another standard tracer was calculated. The main objective was to assess the performance of ICG alone compared with a standard tracer combination in terms of rates of SNB identification along with procedural node positivity rates. Statistical analysis employed Chi-Square test, Fisher’s Exact test, and logistic regression to determine differences between groups. Results: A total of 100 patients were randomized between March and December 2022 with 3 patients excluded from analysis (non-receipt of treatment allocation). Amongst evaluable patients (n=97), the overall SNB identification rate was 96.9% and by tracer category as follows: ICG alone = 97.9% (46/47); ICG + RI = 100% (25/25); ICG + blue dye = 92% (23/25). For cohort 1, the procedural node positivity rates were 17% for ICG alone and 18% for ICG + RI with corresponding figures of 12% for ICG alone and 20% for ICG + blue dye for cohort 2. Mean procedural node retrieval per case was 2.5 in ICG alone Vs ICG + Blue Dye and 2.3 in ICG alone Vs ICG/RI cohorts. There were no significant differences (p&amp;gt;0.05) in performance of ICG alone or combined with a standard tracer, with ICG alone being non-inferior in terms of procedural and nodal detection rates. Similar conclusions were reached from a secondary analysis adjusting for BMI, age and mode of detection (screening/symptomatic). Conclusion: ICG fluorescence imaging permits real-time visualisation of lymphatics and gives an additional dimension to SNB that appears safe versus the competitive alternatives. These results confirm high sensitivity for fluorescence localisation alone for SNB with comparable performance to combined methods with blue dye or RI. The fluorochrome ICG is reliable as a sole tracer and avoids potential drawbacks of blue dye and RI including staining, allergic reactions, availability and costs. Citation Format: Vassilis Pitsinis, Rahul Kanitkar, Alessio Vinci, Emad Elseedawy, Laura Canna, John R Benson. Results of a prospective randomised multicentre study comparing indocyanine green (ICG) fluorescence combined with a standard tracer versus ICG alone for sentinel lymph node biopsy in early breast cancer: The INFLUENCE Trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-02.

Rehabilitation and Return to Play Protocols After Anterior Cruciate Ligament Reconstruction in Soccer Players: A Systematic Review.

Rehabilitation after anterior cruciate ligament ACL reconstruction (ACLR) is crucial for safe return to play (RTP) and reducing the chances of a reinjury. Yet, there is no consensus on the ideal functional tests to assess rehabilitation progress in soccer players after ACLR. The primary objective was to highlight the existing gap in the literature concerning the most effective standardized rehabilitation protocols and testing for facilitating successful RTP among soccer players. Systematic review; Level of evidence, 4. A systematic review using PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) was conducted. Inclusion criteria encompassed original studies (level of evidence 1-4) that examined rehabilitation protocols, metrics of knee rehabilitation, and clinical outcomes after ACLR in soccer players. This review incorporated 23 studies, predominantly retrospective case series, with a total number of 874 soccer players who underwent ACLR and rehabiliation. 5 (21.7%) studies utilized an accelerated rehabilitation protocol, while 7 (30.4%) of studies utilized a criterion-based rehabilitation. A wide heterogeneity of data was extracted including functional tests of rehabilitation and RTP such as strength test batteries, hop test batteries, and movement quality assessments. Of the 23 selected studies, 2 (8.7%) used all 3 test batteries, 8 (34.8%) used 2 test batteries, 12 (52.2%) used 1 test battery, and 1 (4.3%) used 0 of the test batteries. The mean time between surgery and RTP ranged from 3 to 8 months with only 2 (8.7%) studies reporting complications after ACLR. Lastly, out of the total studies examined, 9 (39.1%) assessed patient-reported outcome measures (PROMs), all of which demonstrated significant improvement from the initial assessment to the final follow up. Soccer-specific rehabilitation after ACLR lacks standardization. Even though many studies have assessed protocols for optimal RTP and reduced secondary ACL injuries, there is a gap in the literature regarding the most effective protocols and RTP testing. The methodology reported by Kyritsis et al could serve as a foundation for future prospective randomized multicenter studies to establish a standard rehabilitation protocol and enable a successful return to soccer.

Anterolateral versus anteromedial plate osteosynthesis of midshaft humeral fractures; is there a difference in the rates of iatrogenic radial nerve palsy?

The anterolateral (AL) and anteromedial (AM) surfaces of the humerus are typically used for plate placement during plate osteosynthesis of midshaft humeral fractures via the anterolateral approach. The purpose of this study was to determine if a significant difference exists in the rates of iatrogenic radial nerve palsy (IRNP) following either AL or AM humeral fracture plating. The research question is stated as follows: is anteromedial plating of humeral fractures associated with lower rates of IRNP when compared with anterolateral plating? This multicenter prospective randomized study was undertaken following ethical review and approval with eligible patients who had midshaft humeral fractures or nonunions randomized into 2 groups, viz AL plate osteosynthesis group and AM plate osteosynthesis group. Following diagnostic and preoperative evaluation, patients had open plate osteosynthesis through the anterolateral approach with plate placement according to their study groups. Post-operatively, they were assessed for IRNP while obtained data was analyzed with SPSS version 23 and inter-group differences with P values less than 0.05 were considered statistically significant. Eighty-five eligible patients participated in the study with 43 patients in Group A (AL plate osteosynthesis group) and 42 patients in Group B (AM plate osteosynthesis group). The observed inter-group differences with regard to gender distribution, mean age and clinical diagnosis; acute fracture (AF) versus nonunion were not statistically significant. Furthermore, four (9.3%) patients amongst the 43 patients in Group A (AL plate osteosynthesis group) developed IRNP while two (4.8%) patients amongst the 42 patients in Group B (AM plate osteosynthesis group) had IRNP. The inter-group difference with regard to rates of IRNP was not statistically significant (P = 0.694). This study found that (in contrast to previous studies) there was no significant difference in the rates of IRNP following either open anterolateral or anteromedial plate osteosynthesis of midshaft humeral fractures through the anterolateral approach. Orthopaedic surgeons should therefore remain cautious when obtaining consent for surgery as well as when performing internal fixation of midshaft humeral fractures to limit medicolegal disputes that may arise from IRNP.

Rational and design of prophylactic cranial irradiation (PCI) and brain MRI surveillance versus brain MRI surveillance alone in patients with limited-stage small cell lung cancer achieving complete remission (CR) of tumor after chemoradiotherapy: a multicenter prospective randomized study

BackgroundProphylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged.MethodsA multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4–6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria.DiscussionBased on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI.

Short-Term Opioid Treatment of Acute Locomotor Pain in Older Adults: Comparison of Effectiveness and Safety between Tramadol and Oxycodone: A Randomized Trial.

We conducted a head-to-head comparison of step 2 (tramadol) and step 3 (oxycodone) of the WHO pain ladder in older adults with moderate to severe acute locomotor pain. Multi-center prospective randomized study. Patients were 70 years or older, admitted to the acute geriatric ward of three hospitals, suffering from acute moderate to severe locomotor pain, and opioid-naive. Patients were randomized into two treatment groups: tramadol versus oxycodone. The Consort reporting guidelines were used. Forty-nine patients were included. Mean numeric rating scale (NRS) decreased significantly between day 0 and 2 of the inclusion in both groups. A sustained significant decrease in mean NRS was seen at day 7 in both groups. Nausea was significantly more prevalent in the tramadol group, with a trend towards a higher prevalence of delirium and falls and three serious adverse events in the same group. Opioid therapy may be considered as a short-term effective treatment for moderate to severe acute locomotor pain in older adults. Oxycodone may possibly be preferred for safety reasons. These results can have implications for geriatric practice, showing that opioids for treatment of acute moderate to severe locomotor pain in older patients are effective and safe if carefully monitored for side effects. Opioid therapy may be considered as a short-term treatment for moderate to severe acute locomotor pain in older adults, if carefully monitored for (side) effects, while oxycodone may possibly be preferred for safety reasons. These results can have implications for daily practice in geriatric, orthopedic, and orthogeriatric wards, as well as in terminal care, more precisely for the treatment of moderate to severe acute locomotor pain in older adults.

A prospective multicenter randomized study comparing the SpineJack system and nonsurgical management with a brace in acute traumatic vertebral fractures: the SPICO study.

The objective of this study was to evaluate the efffectiveness of a titanium vertebral augmentation device (SpineJack system) in terms of back pain, radiological outcomes, and economic burden compared with nonsurgical management (NSM) (bracing) for the treatment of vertebral compression fractures. Complications were also evaluated for both treatment methods. A prospective multicenter randomized study was performed at 9 French sites. Patients (n = 100) with acute traumatic Magerl type A1 and A3.1 vertebral fractures were enrolled and randomized to treatment with the SpineJack system or NSM consisting of bracing and administration of pain medication. Participants were monitored at admission, during the procedure, and at 1, 12, and 24 months after treatment initiation. Primary outcomes included visual analog scale back pain score, and secondary outcomes included disability (Oswestry Disability Index [ODI] score), health-related quality of life (EQ-5D score), radiological measures (vertebral kyphosis angle [VKA] and regional traumatic angulation [RTA]), and economic outcomes (costs, procedures, hours of help, and time to return to work). Ninety-five patients were included in the analysis, with 48 in the SpineJack group and 47 in the NSM group. Back pain improved significantly for all participants with no significant differences between groups. ODI and EQ-5D scores improved significantly between baseline and follow-up (1, 12, and 24 months) for all participants, with the SpineJack group showing a larger improvement than the NSM group between baseline and 1 month. VKA was significantly lower (p < 0.001) (i.e., better) in the SpineJack group than in the NSM group at 1, 12, and 24 months of follow-up. There was no significant change over time in RTA for the SpineJack group, but the NSM group showed a significant worsening in RTA over time. SpineJack treatment was associated with higher costs than NSM but involved a shorter hospital stay, fewer medical visits, and fewer hours of nursing care. Time to return to work was significantly shorter for the SpineJack group than for the NSM group. There were no significant differences in complications between the two treatments. Overall, there was no statistical difference in the primary outcomes between the SpineJack treatment group and the NSM group. In terms of secondary outcomes, SpineJack treatment was associated with better radiological outcomes, shorter hospital stays, faster return to work, and fewer hours of nursing care.

Validity of the modified Rankin Scale in patients with aneurysmal subarachnoid hemorrhage: a randomized study

PurposeThe modified Rankin Scale (mRS), a clinician-reported outcome measure of global disability, has never been validated in patients with aneurysmal subarachnoid hemorrhage (aSAH). The aims of this study are to assess: (1) convergent validity of the mRS; (2) responsiveness of the mRS; and (3) the distribution of mRS scores across patient-reported outcome measures (PROMs).MethodsThis is a prospective randomized multicenter study. The mRS was scored by a physician for all patients, and subsequently by structured interview for half of the patients and by self-assessment for the other half. All patients completed EuroQoL 5D-5L, RAND-36, Stroke Specific Quality of Life scale (SS-QoL) and Global Perceived Effect (GPE) questionnaires. Convergent validity and responsiveness were assessed by testing hypotheses.ResultsIn total, 149 patients with aSAH were included for analysis. The correlation of the mRS with EQ-5D-5L was r = − 0.546, while with RAND-36 physical and mental component scores the correlation was r = − 0.439and r = − 0.574 respectively, and with SS-QoL it was r = − 0.671. Three out of four hypotheses for convergent validity were met. The mRS assessed through structured interviews was more highly correlated with the mental component score than with the physical component score of RAND-36. Improvement in terms of GPE was indicated by 83% of patients; the mean change score of these patients on the mRS was − 0.08 (SD 0.915). None of the hypotheses for responsiveness were met.ConclusionThe results show that the mRS generally correlates with other instruments, as expected, but it lacks responsiveness. A structured interview of the mRS is best for detecting disabling neuropsychological complaints.RegistrationURL: https://trialsearch.who.int; Unique identifier: NL7859, Date of first administration: 08-07-2019

Surgical reconstruction of chest wall instability : Indications, contraindications and timing of surgery

The impact of energy on the thorax can lead to serial rib fractures, sternal fractures, the combination of both and to injury of intrathoracic organs depending on the type, localization and intensity. Sometimes this results in chest wall instability with severe impairment of the respiratory mechanics. In the last decade the importance of surgical chest wall reconstruction in cases of chest wall instability has greatly increased. The evidence for asurgical approach has in the meantime been supported by prospective randomized multicenter studies, multiple retrospective data analyses and meta-analyses based on these studies, including aCochrane review. The assessment of form and severity of the trauma and the degree of impairment of the respiratory mechanism are the basis for astructured decision on an extended conservative or surgical reconstructive strategy as well as the timing, type and extent of the operation. The morbidity (rate of pneumonia, duration of intensive care unit stay and mechanical ventilation) and fatality can be reduced by atimely surgery within 72 h after trauma. In this article the already established and evidence-based algorithms for surgical chest wall reconstruction are discussed in the context of the current evidence.

NCOG-14. EFFECT OF CHOLINE ALPHOSCERATE ON THE SURVIVAL OF GLIOBLASTOMA PATIENTS

Abstract Cognitive impairment often occurs in glioblastoma (GBM) patients due to the tumor itself and treatment side effects. Choline alphoscerate (L-alpha-glycerylphosphorylcholine, GPC) is frequently used to compensate for cognitive impairment in GBM patients. This study was conducted to determine whether GPC affects the overall survival (OS) and progression-free survival (PFS) of GBM patients. From 2011 to 2020, 187 isocitrate dehydrongenase (IDH)-wild-type GBM patients were analyzed. The patients were classified based on whether GPC was continuously used for at least 3 or 12 months (mos) after GBM diagnosis. Although GPC usage (≥3 mos) did not make significant differences in survival extension, median OS in the long-term GPC group (≥12 mos) was longer with statistical significance, compared to the control group (&amp;lt; 12mos)(38.3 vs 24.0 mos, p=0.004). In addition to younger age, supratentorial location, complete resection, and MGMT promoter methylation, long-term use of GPC (≥12 mos) was significantly associated with longer OS in multivariate analysis (p = 0.019, hazard ratio [HR] 0.532, 95% confidence interval [CI] 0.314–0.900). Despite the limitations of this study, long-term GPC use was possibly associated with prolonged survival in GBM patients. Multi-center prospective randomized studies with a large number of patients are needed to validate these findings.

On-demand Versus Continuous Maintenance Treatment With a Proton Pump Inhibitor for Mild Gastroesophageal Reflux Disease: A Prospective Randomized Multicenter Study.

It remains unclear which maintenance treatment modality is most appropriate for mild gastroesophageal reflux disease (GERD). We aimed to compare on-demand treatment with continuous treatment using a proton pump inhibitor (PPI) in the maintenance treatment for patients with non-erosive GERD or mild erosive esophagitis. Patients whose GERD symptoms improved after 4 weeks of standard dose PPI treatment were prospectively enrolled at 25 hospitals. Subsequently, the enrolled patients were randomly assigned to either an on-demand or a continuous maintenance treatment group, and followed in an 8-week interval for up to 24 weeks. A total of 304 patients were randomized to maintenance treatment (continuous, n = 151 vs on-demand, n = 153). The primary outcome, the overall proportion of unwillingness to continue the assigned maintenance treatment modality, failed to confirm the non-inferiority of on-demand treatment (45.9%) compared to continuous treatment (36.1%). Compared with the on-demand group, the GERD symptom and health-related quality of life scores significantly more improved and the overall satisfaction score was significantly higher in the continuous treatment group, particularly at week 8 and week 16 of maintenance treatment. Work impairment scores were not different in the 2 groups, but the prescription cost was less in the on-demand group. Serum gastrin levels significantly elevated in the continuous treatment group, but not in the on-demand group. Continuous treatment seems to be more appropriate for the initial maintenance treatment of non-erosive GERD or mild erosive esophagitis than on-demand treatment. Stepping down to on-demand treatment needs to be considered after a sufficient period of continuous treatment.

OR20-06 Diagnosing Central Diabetes Insipidus Using Copeptin Upon Hypertonic Saline Versus Arginine Stimulation

Abstract Disclosure: J. Refardt: None. C. Atila: None. I.O. Chifu: None. E. Ferrante: None. Z. Erlic: None. J.B. Drummond: None. B. Mantovani: None. R. Drexhage: None. C.O. Sailer: None. A. Widmer: None. S. Felder: None. A.S. Powlson: None. N. Hutter: None. D. Vogt: None. M. Gurnell: None. B. Rocha: None. J. Hofland: None. F. Beuschlein: None. M. Fassnacht: None. B.F. Winzeler: None. M. Christ-Crain: None. Background: The main challenge in the diagnosis of central diabetes insipidus (cDI) is its distinction against primary polydipsia (PP). Hypertonic saline stimulated copeptin has a high diagnostic accuracy of 97%, but comprises discomfort for patients and requires close sodium monitoring. Arginine stimulated copeptin showed similar diagnostic accuracy of 93% with better tolerability, but a head-to-head comparison is lacking. We hypothesized that arginine stimulated copeptin is non-inferior (non-inferiority margin 10%) to hypertonic saline stimulated copeptin for the diagnosis of cDI. Methods: In this prospective randomized multicentre study conducted between 2018-2022 in seven tertiary medical centres, consecutive patients with cDI and PP underwent diagnostic evaluation with hypertonic saline and arginine stimulation. Serum copeptin levels were measured at sodium-level of &amp;gt;149 mmol/L after hypertonic saline and 60 minutes after arginine infusion, respectively. The final diagnosis was made after treatment response assessment at three-month follow-up blinded to copeptin levels. The main outcome measure was the overall diagnostic accuracy using the pre-defined copeptin cut-off of 4.9 pmol/L for hypertonic saline and 3.8 pmol/L for arginine stimulation. Results: 158 patients underwent both tests, of which 69 (44%) were diagnosed with cDI and 89 (56%) with PP. Forty-one (59%) patients had a complete and 28 (41%) patients had partial cDI. The diagnostic accuracy [95% CI] to differentiate patients with cDI from patients with PP was 95.6% [91.1,97.8] for hypertonic saline stimulated copeptin compared to 74.4% [67.0, 80.6] for arginine stimulated copeptin. Accordingly, arginine stimulation was inferior to hypertonic saline stimulation (estimated difference [95% CI] -21.2% [-28.7, -14.3]). Side effects were less frequent and less severe under arginine stimulation, resulting in a clear 72% of patients preferring the arginine stimulation over hypertonic saline stimulation. In addition, arginine stimulated copeptin of 3.0 pmol/L diagnosed cDI with a specificity of 90.9% (sensitivity of 59.5%), while a cut-off of 5.2 pmol/L diagnosed PP with a specificity of 91.4% (sensitivity of 56.4%). Conclusion: In the diagnostic evaluation of cDI, copeptin upon hypertonic saline stimulation was superior to arginine stimulation. Arginine stimulation can be used as a first well-tolerated test diagnosing &amp;gt;50% of patients with high accuracy, but hypertonic saline stimulation remains the test with the highest diagnostic accuracy. Presentation: Saturday, June 17, 2023

BOB-ACG study: Pulse methylprednisolone to prevent bilateral ophthalmologic damage in giant cell arteritis. A multicentre retrospective study with propensity score analysis

IntroductionGiant cell arteritis (GCA) is complicated in 10 to 20% of cases by permanent visual ischemia (PVI). International guidelines advocate the use of intravenous pulse of methylprednisolone from 250 to 1000mg per day, for three days, followed by oral prednisone at 1mg/kg per day. The aim of this study is to assess whether this strategy significantly reduces the risk of early PVI of the second eye, compared with direct prednisone at 1mg/kg per day. MethodsWe conducted a multicentre retrospective observational study over the past 15 years in 13 French hospital centres. Inclusion criteria included: new case of GCA; strictly unilateral PVI, prednisone at dose greater than or equal to 0.9mg/kg per day; for the intravenous methylprednisolone (IV-MP) group, total dose between 900 and 5000mg, close follow-up and knowledge of visual status at 1 month of treatment, or earlier, in case of contralateral PVI. The groups were compared on demographic, clinical, biological, iconographic, and therapeutic parameters. Statistical analysis was optimised using propensity scores. ResultsOne hundred and sixteen patients were included, 86 in the IV-MP group and 30 in the direct prednisone group. One patient in the direct prednisone group and 13 in the IV-MP group bilateralised, without significant difference between the two strategies (3.3% vs 15.1%). Investigation of the association between IV-MP patients and contralateral PVI through classical logistic regression, matching or stratification on propensity score did not show a significant association. Weighting on propensity score shows a significant association between IV-MP patients and contralateral PVI (OR=12.9 [3.4; 94.3]; P<0.001). Improvement in visual acuity of the initially affected eye was not significantly associated with IV-MP (visual acuity difference 0.02 vs –0.28 LogMar), even in the case of early management, i.e., within the first 48hours after the onset of PVI (n=61; visual acuity difference –0.11 vs 0.25 LogMar). Complications attributable to corticosteroid therapy in the first month were significantly more frequent in the IV-MP group (31.8 vs 10.7%; P<0.05). DiscussionOur data do not support the routine use of pulse IV-MP for GCA complicated by unilateral PVI to avoid bilateral ophthalmologic damage. It might be safer to not give pulse IV-MP to selected patients with high risks of glucocorticoids pulse side effects. A prospective randomised multicentre study comparing pulse IV-MP and prednisone at 1mg/kg per day is desirable.