Multicenter Intervention Study Research Articles

#443 LEVIL evaluates the impact of HDx on HR-QoL and symptoms, including durability-of-effect and variability

Abstract Background and Aims Current hemodialysis (HD), utilizing conventional high-flux dialyzers, is handicapped by clearance limitations (larger-sized uremic toxins), which contribute to poor health-related quality-of-life (HR-QoL) and symptom-burden. Recent international consensus and guideline-setting efforts have explicitly prioritized identification and management of symptoms and subjective experience, whilst also acknowledging the lack of tools available to fully appreciate and continuously monitor these challenges. This study aimed to utilize dynamic patient-reported-outcome-measurement tool (PROM), London Evaluation of Illness (LEVIL-developed in-house), to iteratively interrogate patient-experience and to confirm previously reported HR-QoL benefits of the use of expanded hemodialysis (HDx) using medium cut-off dialyzer (extending the spectrum of uremic toxins being addressed). Furthermore, this study aimed to extend appreciation of effects on patient subjective experience to include durability-of-effects, variability of symptom-measures and impact of HDx withdrawal. Methods We conducted a multi-centre interventional study in 47 patients established on conventional thrice weekly centre-based HD in Ontario, Canada. Study protocol was 15-months in length with five phases 1) one-month observation (high-flux-HD), 2) three-months HDx 3) two-month wash-out (high-flux-HD), 4) six-months HDx, 5) three-month wash-out (high-flux-HD). HR-QoL and symptom-burden were evaluated using LEVIL throughout study. Results HDx-therapy improved HR-QoL [p 0.0006 (19% from baseline)] and a variety of symptoms including general wellbeing [p 0.005 (23%)], energy [p 0.004 (33%)], sleep-quality [p 0.001 (33%)], pruritus [0.003 (30%)], pain [p 0.01 (19%)], restless leg syndrome [p 0.0006 (15%)], mood [p 0.02 (12%)], appetite [ p 0.03 (9%)], breathlessness [p 0.001 (9%)], and HD-recovery [p 0.004 (26%)]. Response was more pronounced in those with poorer HR-QoL and higher symptom-burden. Improvements were durable over time with continued use with less symptom-variability (range 10-35% improvement). Improvements diminished gradually with return to high-flux-HD. The drivers of poor HR-QoL were largely general-wellbeing, energy, sleep-quality, pruritus, and bodily pain. Conclusion Use of a dynamic PROM effectively allowed appreciation of HR-QoL burden in HD-patients. Use of HDx-therapy results in improved patient subjective outcomes that are durable and associated with significantly lower variation in important symptom-domains than patients experience with receiving conventional high-flux-HD.

Implementation of lung ultrasonography by general practitioners for lower respiratory tract infections: a feasibility study

Objective To evaluate the feasibility of lung ultrasonography (LUS) performed by novice users’ general practitioners (GPs) in diagnosing lower respiratory tract infections (LRTIs) in primary health care settings. Design A prospective interventional multicenter study (December 2019–March 2020). Settings and subjects Patients aged >3 months, suspected of having LRTI consulting in three different general practices (GPs) (rural, semirural and urban) in France. Main outcome measures Feasibility of LUS by GPs was assessed by (1) the proportion of patients where LUS was not performed, (2) technical breakdowns, (3) interpretability of images by GPs, (4) examination duration and (5) patient perception and acceptability. Results A total of 151 patients were recruited, and GPs performed LUS for 111 (73.5%) patients (LUS group). In 99.1% (n = 110) of cases, GPs indicated that they were able to interpret images. The median [IQR] exam duration was 4 [3–5] minutes. LRTI was diagnosed in 70.3% and 60% of patients in the LUS and no-LUS groups, respectively (p = .43). After LUS, GPs changed their diagnosis from ‘other’ to ‘LRTI’ in six cases (+5.4%, p < .001), prescribed antibiotics for five patients (+4.5%, p = .164) and complementary chest imaging for 10 patients (+9%, p < .001). Patient stress was reported in 1.8% of cases, 81.7% of patients declared that they better understood the diagnosis, and 82% of patients thought that the GP diagnosis was more reliable after LUS. Conclusions LUS by GPs using handheld devices is a feasible diagnostic tool in primary health care for LRTI symptoms, demonstrating both effectiveness and positive patient reception. Trial Registration Number Clinicaltrial.gov: NCT04602234, 20/10/2020.

Clinical effectiveness of drop-in mental health services at paediatric hospitals: A non-randomised multi-site study for children and young people and their families - study protocol.

Despite the high prevalence of mental health difficulties in children and young people with long-term health conditions (LTCs), these difficulties and experiences are often overlooked and untreated. Previous research demonstrated the effectiveness of psychological support provided via a drop-in mental health centre located in a paediatric hospital. The aim of this prospective non-randomised single-arm multi-centre interventional study is to determine the clinical effectiveness of drop-in mental health services when implemented at paediatric hospitals in England. It is hypothesised that families who receive psychological interventions through the drop-in services will show improved emotional and behavioural symptoms. Outcomes will be measured at baseline and at 6-month follow-up. The primary outcome is the difference in the total difficulties score on the Strengths and Difficulties Questionnaire (SDQ) reported by parent or child at 6 months. Secondary outcomes include self and parent reported Paediatric Quality of Life Inventory (PedsQL), self-reported depression (PHQ-9) and anxiety measures (GAD-7) and family satisfaction (CSQ-8). This trial aims to determine the clinical effectiveness of providing psychological support in the context of LTCs through drop-in mental health services at paediatric hospitals in England. These findings will contribute to policies and practice addressing mental health needs in children and young people with other long-term health conditions. ISRCTN15063954, Registered on 9 December 2022.

Training in optical diagnosis in community hospitals is associated with improved recognition and treatment of T1 CRC: a prospective multicenter intervention study (OPTICAL II).

Recognition of T1 colorectal cancer (CRC) is difficult, with sensitivities of 35-60% in Western countries. We evaluated the real-life effects of the implementation of the OPTICAL model, a recently developed structured and validated prediction model, in Dutch community hospitals. In this prospective multicenter study, 383 endoscopists from 40 hospitals were invited to follow an e-learning on the OPTICAL-model, to increase sensitivity for detecting T1CRC in non-pedunculated polyps. Next, real-life recognition of T1CRC was evaluated in 25 hospitals. Endoscopic and pathologic reports of T1CRCs detected during the next year were collected retrospectively while endoscopists were unaware of this evaluation. Sensitivity for recognition of T1CRC, R0 resection rate, and treatment modality were compared for trained vs. untrained endoscopists and for recognised vs. unrecognised T1CRCs. Within 1 year after the e-learning 251 endoscopists detected 528 non-pedunculated T1CRCs, 118 (47%) of the endoscopist were trained. T1CRCs had a median size of 20mm and were mainly located in the distal colorectum (66%). Trained endoscopists recognised T1CRCs more frequently than untrained endoscopists (sensitivity 74% vs. 62%; mixed model analysis OR 2.90; 95%CI 1.54-5.45. A higher rate of R0 resection was seen for T1CRCs detected by trained endoscopists (69% vs. 56%, OR 1.73; 95%CI 1.03-2.91). Training in optical recognition of T1CRCs in community hospitals was associated with an increase in sensitivity for T1CRCs. Recognition led to a higher rate of en bloc local excision, resulting in higher R0-resection rates. This may be an important step towards more organ-preserving strategies.

Tripartite prehabilitation of patients with acute myeloid leukaemia and high-risk myelodysplastic syndromes during intensive chemotherapy before allogeneic haematopoietic stem cell transplantation (COHABILIT): protocol for an innovating prospective multicentre study

ObjectivesAcute myeloid leukaemia (AML) and high-risk myelodysplastic syndromes (MDS) are often treated with intensive chemotherapy followed by allogeneic haematopoietic stem cell transplantation (allo-HSCT). The pretransplant treatment results in a general...

The Impact of Symptoms of Depression, Anxiety, and Low Stress-Coping Capacity on the Effects of Telephone Follow-Up on Recovery Measures After Hysterectomy.

To investigate if symptoms of depression, anxiety, and stress-coping capacity have an impact on the effect of telephone follow-up (TFU) on trajectories of six recovery measures after hysterectomy and influence the occurrence of unplanned telephone contacts (uTCs) and unplanned visits (uVs) to health care providers. A post hoc nonrandomized analysis of participants enrolled in a randomized, four-armed, single-blinded, controlled multicenter intervention study comprising 487 women where the women were allocated 1:1:1:1 to one of four TFU models. The Swedish Postoperative Symptom Questionnaire (SPSQ) and two health-related quality of life questionnaires, the EuroQoL-5 dimension with three levels (EQ-5 D-3 L) and the Short-Form-Health Survey (SF-36) assessed the recovery measures. The six recovery measures consisted of the EQ-5D-3L health index, the SF-36 physical component summary (PCS) and mental component summary (MCS), and the maximum and average pain intensity, and symptom sum score obtained from the SPSQ. Psychological distress was evaluated by the psychometric forms, the Hospital Anxiety and Depression Scale and the Stress Coping Inventory. The occurrence of uTC and uV within the 6 weeks of follow-up was registered. Preoperative anxiety, depression, and stress-coping capacity did not modify the effects of the TFU models on the trajectories of the recovery measures, although anxiety and depression were strongly associated with all six recovery measures. uTCs, but not uVs occurred more often in the women with anxiety. Preoperative anxiety, depression, and stress-coping capacity did not appear to influence the effects of TFU contacts on the recovery measures after hysterectomy. Preoperative anxiety seemed to increase the occurrence of uTC. Clinical Trials Registration: ClinicalTrials.gov (NCT01526668).

A multi-center interventional study to assess pharmacokinetics, effectiveness, and tolerability of prolonged-release tacrolimus after pediatric kidney transplantation: study protocol for a prospective, open-label, randomized, two-phase, two-sequence, single dose, crossover, phase III b trial.

Tacrolimus, a calcineurin inhibitor (CNI), is currently the first-line immunosuppressive agent in kidney transplantation. The therapeutic index of tacrolimus is narrow due to due to the substantial impact of minor variations in drug concentration or exposure on clinical outcomes (i.e., nephrotoxicity), and it has a highly variable intra- and inter-individual bioavailability. Non-adherence to immunosuppressants is associated with rejection after kidney transplantation, which is the main cause of long-term graft loss. Once-daily formulations have been shown to significantly improve adherence compared to twice-daily dosing. Envarsus®, the once-daily prolonged-release formulation of tacrolimus, offers the same therapeutic efficacy as the conventional twice-daily immediate-release tacrolimus formulation (Prograf®) with improved bioavailability, a more consistent pharmacokinetic profile, and a reduced peak to trough, which may reduce CNI-related toxicity. Envarsus® has been approved as an immunosuppressive therapy in adults following kidney or liver transplantation but has not yet been approved in children. The objective of this study is to evaluate the pharmacokinetic profile, efficacy, and tolerability of Envarsus® in children and adolescents aged ≥ 8 and ≤ 18 years to assess its potential role as an additional option for immunosuppressive therapy in children after kidney transplantation. The study is designed as a randomized, prospective crossover trial. Each patient undergoes two treatment sequences: sequence 1 includes 4 weeks of Envarsus® and sequence 2 includes 4 weeks of Prograf®. Patients are randomized to either group A (sequence 1, followed by sequence 2) or group B (sequence 2, followed by sequence 1). The primary objective is to assess equivalency between total exposure (of tacrolimus area under the curve concentration (AUC0-24)), immediate-release tacrolimus (Prograf®) therapy, and prolonged-release tacrolimus (Envarsus®) using a daily dose conversion factor of 0.7 for prolonged- versus immediate-release tacrolimus. Secondary objectives are the assessment of pharmacodynamics, pharmacogenetics, adherence, gut microbiome analyses, adverse events (including tacrolimus toxicity and biopsy-proven rejections), biopsy-proven rejections, difference in estimated glomerular filtration rate (eGFR), and occurrence of donor-specific antibodies (DSAs). This study will test the hypothesis that once-daily prolonged-release tacrolimus (Envarsus®) is bioequivalent to twice-daily intermediate-release tacrolimus after pediatric kidney transplantation and may reduce toxicity and facilitate medication adherence. This novel concept may optimize immunosuppressive therapy for more stable graft function and increased graft survival by avoiding T-cell mediated and/or antibody-mediated rejection due to improved adherence. In addition, the study will provide data on the pharmacodynamics and pharmacogenetics of prolonged-release tacrolimus in children and adolescents. EUDRA-CT 2019-003710-13 and ClinicalTrial.gov, identifier NCT06057545.

What is the Opinion of the Health Care Personnel Regarding the Use of Different Assistive Tools to Improve the Quality of Neonatal Resuscitation?

It is important to determine whether the use of different quality improvement tools in neonatal resuscitation is well-received by health care teams and improves coordination and perceived quality of the stabilization of the newborn at birth. This study aimed to explore the satisfaction of personnel involved in resuscitation for infants under 32 weeks of gestational age (<32 wGA) at birth with the use of an assistance toolkit: Random Real-time Safety Audits (RRSA) of neonatal stabilization stations, the use of pre-resuscitation checklists, and the implementation of briefings and debriefings. A quasi-experimental, prospective, multicenter intervention study was conducted in five level III-A neonatal intensive care units in Madrid (Spain). The intervention involved conducting weekly RRSA of neonatal resuscitation stations and the systematic use of checklists, briefings, and debriefings during stabilization at birth for infants <32 wGA. The satisfaction with their use was analyzed through surveys conducted with the personnel responsible for resuscitating these newborns. These surveys were conducted both before and after the intervention phase (each lasting 1 year) and used a Likert scale response model to assess various aspects of the utility of the introduced assistance tools, team coordination, and perceived quality of the resuscitation. Comparison of data from 200 preintervention surveys and 155 postintervention surveys revealed statistically significant differences (p < 0.001) between the two phases. The postintervention phase scored higher in all aspects related to the effective utilization of these tools. Improvements were observed in team coordination and the perceived quality of neonatal resuscitation. These improved scores were consistent across personnel roles and years of experience. Personnel attending to infants <32 wGA in the delivery room are satisfied with the application of RRSA, checklists, briefings, and debriefings in the neonatal resuscitation and perceive a higher level of quality in the stabilization of these newborns following the introduction of these tools. · RRSA, checklists, briefings, and debriefings improve the quality of neonatal resuscitation at birth.. · These tools, when used together, are well-received and enhance perceived resuscitation quality.. · Perception of utility and quality improvement is consistent across roles and experience..

P679 Anti-TNF de-escalation following a treat-to-target strategy with golimumab therapy intensification to reach continuous clinical response in ulcerative colitis: the In-Target GETAID trial

Abstract Background Achieving deep and continuous remission with tight control could allow de-escalation in patients with UC. The in-TARGET study was a prospective two-phase trial in UC patients initiating golimumab (GLM), that aimed to determine the proportion of patients with continuous clinical response (CCR) and endoscopic remission (ER) after one year of treatment optimization strategy (phase 1); then to assess treatment de-escalation outcome in these patients (phase 2). Methods This was a multicentre prospective interventional study in GETAID centres. The study included adult patients with active UC (Mayo Score ≥6 with an endoscopic subscore ≥2), naive to biologics. In the first part of the study, patients received a conventional GLM regimen, depending on their weight (&amp;lt;80 kg; ≥80 kg). At week 10, primary responders continued with the standard maintenance regimen (50 mg or 100 mg/4 w) and non-primary responders had systematic treatment optimization (&amp;lt;80 kg, GLM 100mg/4 w; ≥80kg, introduction of an immunosuppressant) (Figure 1). In the second part of the study, patients in CCR and in ER (Mayo endoscopic score 0-1) at w 54, had treatment de-escalation: GLM discontinuation for patients receiving 50mg, and dose de-escalation to 50mg for those receiving 100mg. Results A total of 197 patients were included, mean duration of UC was 75.9 (± 95.3) months, the mean total Mayo score was 8.4 (± 1.7). At w 10, 14 patients had stopped treatment for failure, 83 (42.1%) had a primary response, and 100 (50.7%) non-primary responders had treatment optimization. At w 54, 95 (48.2%) patients were still on GLM; of these, 64 (32.5%) patients were in CCR and ER. At w 0 and 10, no factors were associated with CCR + ER at w54. Serum GLM levels after w10 were not associated with CCR and ER at w54. No patient developed anti-GLM antibodies between w0 and w54. Sixty patients participated in the second de-escalation phase of the study: in 18 GLM was discontinued, in 38 GLM dose was de-escalated from 100 to 50mg/4 w, and 4 patients refused dose de-escalation. At w 108, 34/56 (60.7%) patients were in CCR and ER, with no change in treatment. No factors were associated with w108 remission. At w108, 23 patients had relapsed: 4/18 (22.2%) among GLM discontinuations, 19/38 (50%) among patients de-escalated from 100 to 50 mg/4w. During follow-up, no colectomy was reported, and 14 severe non-UC related adverse events occurred (3 severe infections, 2 severe anaemias, and 1 rectal cancer). Conclusion One third of UC patients achieved a CCR with ER at one year with optimized GLM therapy. After de-escalation of GLM, 60% of remitters at one year maintained deep remission at two years. Anti-TNF de-escalation following a treat-to-target strategy could be considered in some UC patients.

Cost Savings and Waste Reduction Through Redispensing Unused Oral Anticancer Drugs

New strategies targeting waste are required to improve financial and ecologic sustainability of expensive therapies, such as oral anticancer drugs, that frequently remain unused by patients. Redispensing unused oral anticancer drugs seems to be a promising strategy when drug quality is guaranteed. To determine the waste reduction and net cost savings attained by redispensing oral anticancer drugs that go unused by patients compared with the standard practice of disposal. The ROAD study was a prospective single-group intervention conducted in the outpatient pharmacies of 4 hospitals in the Netherlands from February 1, 2021, to February 1, 2023, with 12-month follow-up of each patient. Patients with cancer and who had a prescription for an oral anticancer drug that could be stored at room temperature were included. Of 2426 eligible patients, 602 did not consent and 601 did not respond. Data analyses were performed from August 25, 2022, to April 19, 2023. Participants received oral anticancer drugs for use at home in special packaging (ie, sealed packaging with time-temperature indicator), to be returned to the pharmacy should these remain unused. The pharmacy ensured quality of returned drugs based on authenticity, appearance, remaining shelf life and adequate storage temperature. Drugs fulfilling quality requirements were redispensed to other patients. Total waste reduction and mean net annual cost savings per patient compared with the standard practice of disposal. Optimization of cost savings was explored by introducing variations in the quality assurance procedure and patient population. All analyses used the average exchange rate for 2021 €1 = US $1.18. Of 1223 patients with cancer who consented, 1071 participated (median [IQR] age, 70 [62-75] years; 622 [58.1%] were male). In all, 171 patients (16.0%; 95% CI, 13.8%-18.3%) returned 335 unused oral anticancer drug packages. Of the returned drugs, 228 packages were redispensed, which reduced waste by 68.1% (95% CI, 67.7%-68.5%) compared with the standard practice (disposal). Redispensing unused oral anticancer drugs comprised 2.4% (95% CI, 2.2%-2.5%) of total drug costs, providing mean net annual cost savings of US $680 (95% CI, $524-$837) up to $1591 (95% CI, $1226-$2002) per participant. The findings of this multicenter intervention study indicate that redispensing unused oral anticancer drugs is associated with waste reduction and cost savings, which in turn may improve the affordability and sustainability of cancer treatment. World Health Organization International Clinical Trials Registry Platform Identifier: NL9208.

Time to extend the indication for sentinel node biopsy in vulvar cancer? Results from a prospective nationwide Swedish study

ObjectiveTo assess detection rates and negative predictive values of sentinel node biopsy in vulvar squamous cell carcinoma with tumors ≥4 cm, multifocal tumors, and in locally recurrent disease.MethodsBetween December 2019...

Four-week administration of an energy and protein dense oral nutritional supplement improves micronutrient concentrations but does not completely correct deficiencies in institutionalized malnourished older adults.

Poor food intake is common among elderly living in nursing homes, leading to micronutrient deficiency (MD). There are no recommendations for the management of MD in malnourished older adults. We conducted a single arm, open-label, multicenter interventional study in institutionalized malnourished older adults to describe the effect of a 4-week daily energy and protein dense oral nutritional supplementation (ONS, 600 kcal, 30 g protein per unit) containing 50% of the recommended daily micronutrient intake on micronutrient status. Plasma concentrations of vitamins (A, B9, B12, C, E), magnesium (Mg), selenium (Se) and zinc (Zn), and erythrocyte vitamin B9 were measured at baseline and after 4 weeks. Forty-six participants completed the study (age 87.4 ± 6.6). At baseline, the most frequent MD were Se (48%), Zn (35%), Mg (24%) and vitamin C (24%). Plasma concentrations of vitamins B9, B12, C and E, Mg, Se and Zn significantly increased and the proportion of subjects with at least one MD decreased (p = 0.006). However, after 4 weeks, 40% of subjects still had at least one MD. ONS consumption improved micronutrient status but did not correct MD in all participants. Our data suggest that the prescription of vitamin, mineral and trace element supplementation should be considered in institutionalized malnourished older adults in addition to high energy and high protein ONS.

Investigating two mobile just-in-time adaptive interventions to foster psychological resilience: research protocol of the DynaM-INT study.

Stress-related disorders such as anxiety and depression are highly prevalent and cause a tremendous burden for affected individuals and society. In order to improve prevention strategies, knowledge regarding resilience mechanisms and ways to boost them is highly needed. In the Dynamic Modelling of Resilience - interventional multicenter study (DynaM-INT), we will conduct a large-scale feasibility and preliminary efficacy test for two mobile- and wearable-based just-in-time adaptive interventions (JITAIs), designed to target putative resilience mechanisms. Deep participant phenotyping at baseline serves to identify individual predictors for intervention success in terms of target engagement and stress resilience. DynaM-INT aims to recruit N = 250 healthy but vulnerable young adults in the transition phase between adolescence and adulthood (18-27years) across five research sites (Berlin, Mainz, Nijmegen, Tel Aviv, and Warsaw). Participants are included if they report at least three negative burdensome past life events and show increased levels of internalizing symptoms while not being affected by any major mental disorder. Participants are characterized in a multimodal baseline phase, which includes neuropsychological tests, neuroimaging, bio-samples, sociodemographic and psychological questionnaires, a video-recorded interview, as well as ecological momentary assessments (EMA) and ecological physiological assessments (EPA). Subsequently, participants are randomly assigned to one of two ecological momentary interventions (EMIs), targeting either positive cognitive reappraisal or reward sensitivity. During the following intervention phase, participants' stress responses are tracked using EMA and EPA, and JITAIs are triggered if an individually calibrated stress threshold is crossed. In a three-month-long follow-up phase, parts of the baseline characterization phase are repeated. Throughout the entire study, stressor exposure and mental health are regularly monitored to calculate stressor reactivity as a proxy for outcome resilience. The online monitoring questionnaires and the repetition of the baseline questionnaires also serve to assess target engagement. The DynaM-INT study intends to advance the field of resilience research by feasibility-testing two new mechanistically targeted JITAIs that aim at increasing individual stress resilience and identifying predictors for successful intervention response. Determining these predictors is an important step toward future randomized controlled trials to establish the efficacy of these interventions.

Use of left atrial automated functional myocardial imaging to identify patients with paroxysmal atrial fibrillation at high risk of stroke.

Left atrial automated functional myocardial imaging (AFILA) is a new software program for analyzing the structure and function of the left atrium (LA). The present study sought to analyze the correlation between the LA function parameters as measured by AFILA echocardiography and the risk of cerebral ischemic stroke (CIS) in patients with non-valvular paroxysmal atrial fibrillation (NVPAF) to explore the diagnostic value of LA strain in patients with congestive heart failure, hypertension, age of ≥75 years (doubled), diabetes mellitus, stroke or transient ischemic attack (TIA) (doubled), age of 65-74 years, and sex category (female) (CHA2DS2-VASc) scores of <2. A total of 205 patients with NVPAF were included in the study and divided into the no-CIS group (154 patients) and the CIS group (51 patients). The baseline clinical data for the 2 groups were analyzed, and routine echocardiography examinations were performed. AFILA was used to evaluate the LA function of all the patients. Compared to the no-CIS group, the LA emptying fraction and the LA reservoir strain were decreased, the LA contractile strain (S_CT) was increased, and the S_CT value changed from negative to positive in the CIS group, and the difference between the 2 groups were statistically significant (P<0.001). However, there were no significant differences in the volume at the onset of LA contraction, LA evacuation volume, LA minimum volume, LA maximum volume, and LA conduit strain between the 2 groups. The multifactorial regression analysis showed that age, hypertension, and the S_CT were independently associated risk factors for patients with CIS. After correcting for the clinical factors included in the CHA2DS2-VASc score, the S_CT was shown to predict to NVPAF with stroke [odds ratio (OR): 1.234, 95% confidence interval (CI): 1.101-1.383, P=0.000]. In addition, we included the CHA2DS2-VASc score (instead of age, diabetes, coronary artery disease, and hypertension) in a multiple regression analysis, and found that the S_CT was still significant (OR: 1.252, 95% CI: 1.118-1.402, P=0.000). The difference between the 2 groups in the CHA2DS2-VASc score for the S_CT was statistically significant, especially when the CHA2DS2-VASc score was <2. The S_CT equaled -4.5% was the cut-off value for the presence or absence of CIS in the NVPAF patients, with an area under the curve (AUC) of 0.866, sensitivity of 0.80, and specificity of 0.75 (P<0.0001). Comparison with LA volume parameter, measuring LA strain by AFILA provides a better index for the dynamic assessment of impaired LA function in patients with NVPAF combined with CIS, especially in those with a CHA2DS2-VASc score of <2. In addition, a LA S_CT of >-4.5% is a valuable cut-off for patients with NVPAF. The results of the current study may form the basis for a large prospective multicenter interventional study in which patients with impaired LA S_CT are randomized to receive oral anti-coagulant (OAC) therapy or no OAC therapy for the primary prevention of stroke.

#6780 EFFECTS OF ISONATREMIC DIALYSIS ON INTERDIALYTIC WEIGHT GAIN RELYING ON AN AUTOMATED SODIUM CONTROL ALGORITHM: INTERIM ANALYSIS OF DISON-IRC STUDY

Abstract Background and Aims Sodium (Na) is a major determinant of extracellular fluid volume and osmolarity homeostasis. Chronic fluid overload (FO) is present in 30 to 50% of hemodialysis patients (HD). HD patients are mostly treated with fixed dialysate Na concentration irrespective of plasma Na concentration. This fixed approach tends to displace patient's osmolar set point and stimulates thirst and weight gain. An automated personalized dialysate Na alignment to patient's natremia to avoid unwanted diffusive Na gain and tonicity change induced by HD seems preferable. Several studies exploring individualized dialysate Na prescription have reported inconsistent results. In this prospective interventional multicenter study, we aimed to explore the impact of dialysate Na individualization through isonatremic HD on interdialytic weight gain (IDWG) (primary outcome) and dialytic HD-related symptoms (secondary outcome). For this purpose, we have used the automated “Na Control” option for adjusting dialysate Na to minimize dialysate-plasma sodium gradient and deliver an isonatremic dialysis. Method This is a longitudinal study comparing 2 periods: Period-1 = observational phase (2 months) → Period-2 = isonatremic phase by activation of “Na Control” in isonatremic mode (2 months) → comparison of IDWG between both periods. The embedded “sodium control” option in HD machine was used in all cases of Period-2 to actively align dialysate sodium concentration to natremia and quantify net sodium mass transfer. Results are expressed as mean±SD or median [25th-75th]. Results We present preliminary results obtained through 6 dialysis facilities including 51 patients, 33 (64.7%) females, 75 [65-81] years old, dry weight 71.9 [60.5-78.0] kg. Main findings are as follows: Firstly, an excellent agreement was observed between plasma Na concentrations, measured (laboratory) and estimated (machine) from HD monitor (mean difference before dialysis: 0.05, after dialysis: 0.62); Secondly, plasma Na estimated was as follows: before dialysis plasma Na (137.6 [136.2-139.0] vs 137.2 [136.0-139.3] and after dialysis plasma Na (139.0 [137.6-139.7] vs 137.1 [135.7-138.9]) in Period-1 and Period-2 respectively; Thirdly, the primary outcome (IDWG) as well as the diffusive Na balance were significantly reduced by isonatremic dialysis condition (IDWG: 2.17±0.92 versus 1.95±0.86 kg, p&amp;lt;0,0001; diffusive Na balance (3.9 [1.9-5.1] versus 0.7 [0.0-2.7] g of Na, p&amp;lt;0.0001). Conclusion Isonatremic dialysis condition automatically driven by “Na control” embedded In HD monitor was confirmed safe and easily implemented in clinical workflow. In addition, these preliminary results show that isonatremic dialysis improved dialysis patient perception and significantly reduced IDWG.

Long-Term Intake of Linezolid Elevates Drug Exposure and Reduces Drug Clearance and Elimination in Adults With Drug-Resistant Pulmonary Tuberculosis.

Pharmacokinetic (PK) studies are critical for dose optimization, and there is a paucity of linezolid (LZD) PK data for prolonged use in drug-resistant tuberculosis (DR-TB). Therefore, the authors evaluated the pharmacokinetics of LZD at two-time intervals in DR-TB during long-term use. PK evaluation of LZD was performed at the end of the 8th and 16th weeks of treatment in a randomly selected subset of adult pre-extensively drug-resistant pulmonary tuberculosis patients (n = 18) from a multicentric interventional study (Building Evidence to Advance Treatment of TB/BEAT study; CTRI/2019/01/017310), wherein a daily dose of 600 mg LZD was used for 24 weeks. Plasma LZD levels were measured using a validated high-pressure liquid chromatography (HPLC) method. The LZD median plasma C max was comparable between the 8th and 16th weeks [18.3 mg/L, interquartile range (IQR: 15.5-20.8 and 18.8 mg/L, IQR: 16.0-22.7, respectively)]. However, the trough concentration increased significantly in the 16th week (3.16 mg/L, IQR: 2.30-4.76), compared with the 8th week (1.98 mg/L, IQR: 0.93-2.75). Furthermore, compared with the 8th week, in the 16th week, there was a significant increase in drug exposure (AUC 0-24 = 184.2 mg*h/L, IQR: 156.4-215.8 versus 233.2 mg*h/L, IQR: 187.9-277.2), which corroborated with a longer elimination half-life (6.94 hours, IQR: 5.55-7.99 versus 8.47 hours, IQR:7.36-11.35) and decreased clearance (2.91 L/h, IQR: 2.45-3.33 versus 2.19 L/h, IQR: 1.49-2.78). Long-term daily intake of 600 mg LZD resulted in a significant elevation in trough concentration (>2.0 mg/L) in 83% of the study participants. Furthermore, increased LZD drug exposure may be partly because of decreased clearance and elimination. Overall, the PK data underscore the need for dose adjustment when LZDs are intended for long-term treatment.

The optimal operative protocol to accomplish CO2-EVAR resulting from a prospective interventional multicenter study: Presented at the 2022 Vascular Annual Meeting of the Society for Vascular Surgery, Boston, Massachusetts, June 15-18, 2022.

Objectives: Carbon dioxide (CO2) angiography for endovascular aortic repair (CO2-EVAR) is used to treat abdominal aortic aneurysms (AAAs), especially in patients with chronic kidney disease or allergy to iodinated contrast medium (ICM). However, some technical issues regarding the visualization of the lowest renal artery (LoRA) and the best quality image through angiographies performed from pigtail or introducer sheath are still unsolved. The aim of this study was to analyze different steps of CO2-EVAR to create an operative standardized protocol.

Different patterns in the corneal endothelial cell loss after pars plana and pars limbal insertion of the Baerveldt glaucoma implant

To assess corneal endothelial cell (CE) loss after pars plana (PP) and pars limbal (PL) insertion of a Baerveldt glaucoma implant (BGI). Retrospective multicenter interventional comparative study. We studied central CE loss for 5 years after BGI surgery in 192 eyes. The prevalence of bullous keratopathy (BK) was greater in the PL cohort than in the PP cohort (P=.003). The CE loss after simultaneous PP vitrectomy and tube insertion into the vitreous cavity was 11.9% in the first year, which was greater than that of 2.9% in eyes where the tube was inserted simply into the vitreous cavity after a prior vitrectomy (P=.046). The annual percentage CE loss after the first year decreased unidirectionally in both of those groups and was 1.3% and 1.0% in the fifth year, respectively (P < .001). For limbal insertion, the CE loss in the simple PL cohort was biphasic, decreasing from 10.5% in the first year to 7.0% in the fifth year. Simultaneous cataract and BGI surgery enhanced the CE loss slightly in the first year in the PP and PL cohorts to 13.0% and 14.0%, respectively. However, these increases were not significant (P=.816 and .358, respectively). Low preoperative CE density (P < .001) and insertion site (P=.020) were significant risk factors for the development of BK. CE loss in the PL and PP cohorts was biphasic and unidirectional, respectively. The difference in annual CE loss became evident over time. PP tube implantation may be advantageous when the preoperative CE density is low.

National implementation of an optimal standardised technique for right-sided colon cancer: protocol of an interventional sequential cohort study (Right study)

PurposeMinimally invasive right hemicolectomy (MIRH) is the cornerstone of treatment for patients with right-sided colon cancer. This operation has evolved during recent decades, with many innovations and improvements but this has also resulted in high variability of uptake with subsequent substantial variableness. The aim of this ongoing study is to identify current surgical variations, determine the most optimal and standardised MIRH and nationally train and implement that technique to improve short-term clinical and long-term oncological outcomes.MethodsThe Right study is a national multicentre prospective interventional sequential cohort study. Firstly, current local practice was evaluated. Subsequently, a standardised surgical technique for right-sided colon cancer was determined using the Delphi consensus method, and this procedure was trained during hands-on courses. The standardised MIRH will be implemented with proctoring (implementation cohort), after which the performance will be monitored (consolidation cohort). Patients who will receive a minimally invasive (extended) right hemicolectomy for cT1-3N0-2M0 colon cancer will be included. The primary outcome is patient safety reflected in the 90-day overall complication rate according to the Clavien–Dindo classification. Secondary outcomes will include intraoperative complications, 90-day mortality rate, number of resected tumour-positive lymph nodes, completeness of mesocolic excision, surgical quality score, locoregional and distant recurrence and 5-year overall survival. A total number of 1095 patients (365 per cohort) will be included.DiscussionThe Right study is designed to safely implement the best surgical practice concerning patients with right-sided colon cancer aiming to standardise and improve the surgical quality of MIRH at a national level.Trial registrationClinicalTrials.gov: NCT04889456, May 2021.

Childhood fever and medical students: a multicenter, educational intervention.

Misconceptions and non-evidence-based practices toward childhood fever are reported worldwide. Medical students might be ideal candidates to introduce long-lasting changes in clinical practice. However, no study has gauged the effectiveness of an educational intervention to improve fever management in this population. We conducted an educational, interventional study on childhood fever among final-year medical students. We conducted a prospective, multicenter interventional study employing a pre/post-test design. Participants from three Italian Universities filled in a questionnaire just before the intervention (T0), immediately after (T1), and six months later (T2) in 2022. The intervention was a two-hour lecture focused on the pathophysiology of fever, recommendations for its treatment, and risks associated with improper management. 188 final-year medical students (median age of 26 years, 67% females) were enrolled. Relevant improvements in the criterion for treating fever and conceptions about the beneficial effects of fever were observed at T1 and T2. Similar data were found for the reduction of physical methods advice to decrease body temperature and concerns for brain damage from fever. This study shows for the first time that an educational intervention is effective in changing students' conceptions and attitudes toward fever both in the short and medium term.