Use In Routine Clinical Practice Research Articles

Effectiveness of calcipotriol/betamethasone dipropionate aerosol foam in patients with small versus large plaque psoriasis in routine practice in South Korea.

Small plaque psoriasis is the typical form of chronic plaque psoriasis affecting adults in South Korea. The effectiveness of calcipotriol/betamethasone dipropionate (Cal/BD) aerosol foam for large and small psoriasis plaques has not previously been examined. We performed a post hoc analysis of a recent, 4-week observational study of Cal/BD aerosol foam use in routine clinical practice in South Korea. Investigator Global Assessment response ([IGA] 0/1 at week 4), Patient Global Assessment response ([PaGA] 0/1 at week 4), change in Psoriasis Area and Severity Index (PASI), changes in psoriasis symptom scores, change in the Dermatology Life Quality Index (DLQI), and the proportion of patients achieving DLQI ≤5 were analyzed for patients with small (≤5 cm; n = 131) or large (>5 cm; n = 35) baseline plaque size. IGA response rates were similar for patients with small and large plaques (59.5% and 51.4% respectively). Similarly, there was no significant difference between the small and large groups in mean change in PASI (-2.20 vs -3.34), the proportions of patients with DLQI ≤5 (62.3% vs 54.3%) or PaGA 0/1 (29.2% vs 40.0%). Mean improvements in DLQI (-4.04 vs -6.20) and in psoriasis symptoms including itching (-1.50 vs -2.83), sleep loss (-0.67 vs -1.89), dryness (-1.57 vs -2.97), scaling (-1.21 vs -3.57), and redness (-1.17 vs -3.11) were greater in patients with large plaques than those with small plaques. Itching and DLQI differences were not statistically significant after adjustment for baseline characteristics. Stratification by body surface area affected eliminated statistically significant differences between the groups for most outcomes. In conclusion, this analysis suggests that Cal/BD aerosol foam is an effective, well-accepted treatment for adult patients with the small plaques typical of chronic plaque psoriasis in South Korea, as well as for those with large plaques.

Root Canal Disinfection in Permanent Molars with Apical Lesion by Antimicrobial Photodynamic Therapy: Protocol for a Blind Randomized Clinical Trial.

Objective: The proposed study aims to compare the effectiveness of conventional endodontic treatment (ET) with that of ET associated with antimicrobial photodynamic therapy (aPDT) in patients with apical lesion. Methods: Controlled, double-blind, randomized clinical trial (RCT); superiority study with three parallel arms. Randomization will be conducted in exchange blocks of six, with allocation 1:1:1. The control group will receive conventional ET, while experimental group 1 (EG1) will receive conventional ET + aPDT with laser at 660 nm, fluence of 600 J/cm2; EG2 will receive conventional ET + aPDT with laser at 660 nm, fluence of 1200 J/cm2. The primary outcome will be canal disinfection before treatment, measured by analysis of colony formation (CFU/mL) and the success rate measured after 6 months on the clinical and radiographic evaluations. The mean and standard deviation will be calculated for continuous outcomes, and the CFU/mL mean between groups will be evaluated by ANOVA test. The Chi-squared test will be calculated for binary outcomes. A logistic regression analysis will be performed to assess differences in the success rate between groups, adjusted for the covariates. The Stata 18 software will be used, with a significance threshold of 5%. Conclusions: Few RCTs have evaluated the effectiveness of aPDT in root canal disinfection in patients with permanent dentition presenting apical lesion. New RCTs with larger numbers of participants are needed to support using aPDT as an adjuvant to conventional ET in root canal disinfection for routine use in clinical practice. The trial was registered prospectively in ClinicalTrials.gov (NCT05916859).

Prediction models for postoperative renal function after living donor nephrectomy: a systematic review.

Living-donor nephrectomy (LDN) is the most valuable source of organs for kidney transplantation worldwide. The current preoperative evaluation of a potential living donor candidate does not take into account formal estimation of postoperative renal function decline after surgery using validated prediction models. The aim of this study was to summarize the available models to predict the mid- to long-term renal function following LDN, aiming to support both clinicians and patients during the decision-making process. A systematic review of the English-language literature was conducted following the principles highlighted by the European Association of Urology (EAU) guidelines and following the PRISMA 2020 recommendations. The protocol was registered in PROSPERO on December 10, 2022 (registration ID: CRD42022380198). In the qualitative analysis we selected the models including only preoperative variables. After screening and eligibility assessment, six models from six studies met the inclusion criteria. All of them relied on retrospective patient cohorts. According to PROBAST, all studies were evaluated as high risk of bias. The models included different combinations of variables (ranging between two to four), including donor-/kidney-related factors, and preoperative laboratory tests. Donor age was the variable more often included in the models (83%), followed by history of hypertension (17%), Body Mass Index (33%), renal volume adjusted by body weight (33%) and body surface area (33%). There was significant heterogeneity in the model building strategy, the main outcome measures and the model's performance metrics. Three models were externally validated. Few models using preoperative variables have been developed and externally validated to predict renal function after LDN. As such, the evidence is premature to recommend their use in routine clinical practice. Future research should be focused on the development and validation of user-friendly, robust prediction models, relying on granular large multicenter datasets, to support clinicians and patients during the decision-making process.

Intracoronary imaging to guide percutaneous coronary intervention: from evidence to guidelines.

Despite notable advances in devices and techniques, percutaneous coronary intervention (PCI) is still affected by a substantial number of complications and failure rates. Over the years, the use of intracoronary imaging (ICI) has dramatically improved the understanding of mechanical and technical factors related to successful and failed PCI, becoming a mainstay in complex trans-catheter interventions. However, ICI modalities are invasive, time-consuming, and costly, and a net clinical benefit needs to be shown in order to recommend their routine use in clinical practice. In the past, the lack of evidence from randomized trials has been reflected in the scepticism shown by international guidelines. The recent publication of large randomized clinical trials conducted worldwide has provided new evidence regarding the clinical usefulness of ICI guidance in PCI. The consistent reduction of adverse events achieved in these trials, also demonstrated in an updated meta-analysis, suggested that the use of ICI in PCI is compelling to achieve optimal technical results and better outcomes, especially in complex high-risk interventions. Also considering the burden of information provided by ICI on coronary artery disease, looking from the inside seems today an opportunity that modern cardiology cannot ignore anymore.

External validation of the 2-year mortality prediction tool in hemodialysis patients developed using a Bayesian network.

In recent years, a number of predictive models have appeared to predict the risk of medium-term mortality in hemodialysis patients, but only one, limited to patients aged over 70 years, has undergone sufficiently powerful external validation. Recently, using a national learning database and an innovative approach based on Bayesian networks and 14 carefully selected predictors, we have developed a clinical prediction tool to predict all-cause mortality at 2 years in all incident hemodialysis patients. In order to generalize the results of this tool and propose its use in routine clinical practice, we carried out an external validation using an independent external validation database. A regional, multicenter, observational, retrospective cohort study was conducted to externally validate the tool for predicting 2-year all-cause mortality in incident and prevalent hemodialysis patients. This study recruited a total of 142 incident and 697 prevalent adult hemodialysis patients followed up in one of the eight Association pour l'Utilisation du Rein Artificiel dans la région Lyonnaise (AURAL) Alsace dialysis centers. In incident patients, the 2-year all-cause mortality prediction tool had an area under the receiver curve (AUC-ROC) of 0.73, an accuracy of 65%, a sensitivity of 71% and a specificity of 63%. In prevalent patients, the performance for the external validation were similar in terms of AUC-ROC, accuracy and specificity, but was lower in term of sensitivity. The tool for predicting all-cause mortality at 2 years, developed using a Bayesian network and 14 routinely available explanatory variables, obtained satisfactory external validation in incident patients, but sensitivity was insufficient in prevalent patients.

Efferent methods of therapy for critical illness

Extracorporeal blood purification is intended to eliminate dysregulation of the immune system. The concept of extracorporeal therapy is based on the nonspecific clearance of inflammatory mediators and triggers, which attenuates the systemic expression of inflammatory mediators. The main types of extracorporeal therapy are hemoadsorption and plasma exchange. Hemoadsorption is used primarily as an adjuvant treatment for septic shock and other severe inflammatory conditions, including severe forms of COVID-19 with cytokine storm.
 Reliable data demonstrating the benefit of hemoadsorption in critically ill patientsis is limited. Recommendations for the use of hemoadsorption devices are often based on incomplete data or questionable interpretations of available data. Given the lack of evidence for the benefit of hemoadsorption in the treatment of severe inflammation, sepsis, liver failure and rhabdomyolysis, its routine use in clinical practice is not justified until the mechanisms underlying these findings are fully elucidated.
 Plasma replacement is a potentially life-saving invasive extracorporeal blood purification procedure that replaces plasma with a substitute fluid (saline, albumin solution, fresh frozen plasma, or a combination of these) with the risk of side effects and complications. There is still uncertainty regarding the timing, type of plasma exchange, volume and frequency of plasma filtration. Although plasma replacement is considered to be relatively safe, there is still insufficient evidence to support its inclusion in sepsis treatment protocols.
 Reports of the use of extracorporeal methods in the treatment of patients with severe refractory systemic inflammation provide evidence of decreased levels of inflammatory biomarkers, improved hemodynamic parameters, and decreased organ failure. However, according to the results of randomized clinical trials, extracorporeal therapy does not affect clinical outcomes, and in some even increases mortality. To clarify the effectiveness of extracorporeal therapy, it is necessary to study the mechanisms of interaction of the devices used with target and non-target blood components and large-scale randomized controlled trials assessing the ability of this therapy to improve clinical outcomes.

Reliability testing of the Health of the Nation Outcome Scales 2018.

The Health of the Nation Outcome Scales (HoNOS) is a widely used clinical measure designed to rate and monitor the outcomes of service users accessing specialist mental healthcare. Since its development (in 1996), numerous research studies have confirmed the HoNOS captures the aspects of care that it purports to (validity), and that clinicians' ratings are consistent both over time, and between different raters (reliability). In 2018, the HoNOS was reviewed with updates made to some terminology and other revisions intended to remove ambiguity in the guidance for raters. However, although the new version (HoNOS 2018) was accompanied by a recommendation that its validity and reliability be re-tested this was not undertaken. To our knowledge, this is the first study to re-assess the updated tool's reliability by measuring the level of agreement between different raters. Our findings confirm that there is an acceptable level of consistency between student mental health nurses that have been trained to use the (new) HoNOS 2018. The HoNOS is nationally mandated for use by all specialist mental healthcare providers in the UK. Our findings provide some assurance that, with appropriate update training and monitoring of organisational-level data sets, the original HoNOS glossary can safely be replaced with the HoNOS 2018 to ensure more contemporary routine outcome measurement can occur. INTRODUCTION: The Health of the Nation Outcome Scales (HoNOS) is a well-established clinician rated outcome measure for use in mental health services. Following an international review, an updated version (HoNOS 2018) was published with a recommendation that its psychometric properties be re-tested prior to widespread implementation. To date, only one such study has been published. To test the inter-rater agreement levels for HoNOS 2018. Third-year student mental health nurses received training to complete the HoNOS 2018. Following this timetabled session, they were each invited to independently rate two, randomly selected, videos of (simulated) patient interviews. The resulting data were then analysed to calculate the tool's internal consistency and inter-rater agreement levels. The 55 participants provided 106 ratings from four vignettes. Cronbach's alphas and McDonalds omegas confirmed the revised tool's internal consistency was acceptable. Average measure intraclass correlation coefficients for the four patient vignettes indicated excellent reliability. This study provides initial assurance that the HoNOS 2018 is a reliable clinician rated outcome measure suitable for use in routine clinical practice by relatively inexperienced mental health practitioners with limited training.

Platelet-rich plasma augmentation in anterior cruciate ligament reconstruction: Evidence is still too scattered. A scoping review of randomised controlled trials.

Platelet-rich plasma (PRP) augmentation has been proposed to improve the results of anterior cruciate ligament reconstruction (ACLR). The present study aims to quantify the available evidence to support the use of PRP as biological augmentation in ACLR surgery. A systematic literature search was conducted on the PubMed, Cochrane, Web of Scienceand Embase databases on 10 March2023. Inclusion criteria were randomised controlled trials (RCTs), written in English, addressing PRP augmentation in ACLR surgery, with no time limitation. A scoping review was performed to map the body of literature by examining the evidence related to specific aspects of patients' treatment and evaluation. Risk of bias evaluation was performed with the Cochrane risk-of-bias tool for randomised trials Version 2 (RoB 2), while the quality assessment was performed with the use of the Coleman Score. Out of 983 articles retrieved, 23 RCTs on 943 knees were included in this scoping review. PRP was administered in a liquid form in ninestudies and clotted in 11 studies, while in three studies both liquid and clotted PRP were used. Hamstring auto/allografts were used in 14 studies, patellar tendon auto/allografts were used in eight studiesand one study described ACLR with peroneus longus allografts. The map of the evidence documented high heterogeneity also in terms of surgical technique, objective and subjective outcome measuresand radiological assessment, as well as follow-up times ranging from 1 day to 2 years, with virtually no overlapping data among studies neither in terms of treatments nor evaluations. Risk of bias evaluation showed an overall low quality of the included studies. The available literature addressing PRP augmentation in ACLR is largely scattered. PRP was produced and applied following different procedures, and high variability was detected across the included studies for every aspect of ACLR surgery and evaluation. Currently, a meaningful comparison of the available studies is not possible as the quantification of the literature results is biased by their heterogeneity. Future studies should provide more standardisation to investigate the benefits of biological augmentation in ACL surgery and confirm the promising yet weak evidence of PRP potential as well as the most suitable application modality, before routine use in clinical practice. Levels I and II, scoping review.

The use of LNG-IUS-19.5 mg in daily gynecological routine practice in Germany: data from the Kyleena™ Satisfaction Study (KYSS)

PurposeThe Kyleena™ Satisfaction Study (KYSS) provided the first data on 19.5 mg levonorgestrel-releasing intrauterine system (LNG-IUS-19.5 mg) use in routine clinical practice. Here we report results from the German participants in KYSS.MethodsThis prospective, observational, single-arm cohort study recruited women who independently chose to use LNG-IUS-19.5 mg during routine counseling in Germany. Overall satisfaction and bleeding profile satisfaction, continuation rates, and safety profile were evaluated at 12 months or premature end of observation (EoO).ResultsIn the German study population, LNG-IUS-19.5 mg placement was attempted in 508 women and successful in 506 women. Mean age was 32.3 years, and 60.0% (n = 305/508) were parous. Placement was considered easy and associated with no more than mild pain, even in younger and nulliparous participants. Of those with satisfaction data available, 87.6% (n = 388/443) were satisfied with LNG-IUS-19.5 mg at 12 months/EoO. Satisfaction was similar for parous (86.9%, n = 238/274) and nulliparous (88.8%, n = 150/169) women, and was independent of age, prior contraceptive method, or reason for choosing LNG-IUS-19.5 mg. Most participants (73.6%, n = 299/406) were also satisfied with their bleeding profile at 12 months/EoO, independent of parity, age, prior contraceptive method, presence of amenorrhea or dysmenorrhea severity. The 12-month continuation rate was 84.1% (n = 427/508). Most discontinuations were due to loss to follow-up (8.5%, n = 43/508) or treatment-emergent adverse events (TEAEs) (4.7%, n = 24/508). TEAEs were reported in 12.6% (n = 64) of participants, with 9.3% (n = 47) considered to have an LNG-IUS-19.5 mg-related TEAE.ConclusionOur real-world findings on LNG-IUS-19.5 mg use in German KYSS participants reflected its suitability for a broad population, including young and nulliparous women.Clinical trial registrationNCT03182140 (date of registration: June 2017).

Monitoring of Remotely Reprogrammable Implantable Loop Recorders With Algorithms to Reduce False-Positive Alerts.

Implantable loop recorders (ILRs) are increasingly placed for arrhythmia detection. However, historically, ≈75% of ILR alerts are false positives, requiring significant time and effort for adjudication. The LINQII and LUX-Dx are remotely reprogrammable ILRs with dual-stage algorithms using artificial intelligence to reduce false positives, but their utility in routine clinical practice has not been studied. We identified patients with the LINQII and LUX-Dx who were monitored by the Veterans Affairs National Cardiac Device Surveillance Program between March and June 2022. ILR programming was customized on the basis of implant indication. All alerts and every 90-day scheduled transmissions were manually reviewed. ILRs were remotely reprogrammed, as appropriate, after false-positive alerts or 2 consecutive same-type alerts, unless there was ongoing clinical need for that alert. Outcomes were total number of transmissions and false positives. We performed medical record review to determine if patients experienced any adverse clinical events, including hospitalization and mortality. Among 117 LINQII patients, there were 239 total alerts, 43 (18.0%) of which were false positives. Among 105 LUX-Dx patients, there were 300 total alerts, 115 (38.3%) of which were false positives. LINQIIs were reprogrammed 22 times, resulting in a decrease in median alerts/day from 0.13 to 0.03. LUX-Dx ILRs were reprogrammed 52 times, resulting in a decrease from 0.15 to 0.01 median alerts/day. There were no adverse clinical events that could have been identified by superior or earlier arrhythmia detection. ILRs with artificial intelligence algorithms and remote reprogramming ability are associated with reduced alert burden because of higher true-positive rates than prior ILRs, without missing potentially consequential arrhythmias.

FAST® questionnaire for identifying glaucoma patients at risk for ocular surface disease.

To evaluate the validity and reliability of the new Fast Assessment of the Ocular Surface Trouble (FAST®) questionnaire for identifying glaucoma or ocular hypertension (OHT) patients at risk of ocular surface disease (OSD). A multicenter, international, cross-sectional, epidemiological survey evaluated the most accurate interview items and ocular signs on the initial 14-item version of FAST® to develop a shorter version for routine, quick clinical use. Rasch analysis and least absolute shrinkage and selection operator (LASSO) method was used to reduce the number of items on the questionnaire. Sensitivity and specificity of FAST® were assessed with receiver operating characteristic (ROC) curves for the detection of OSD with the questionnaire and ophthalmic assessment. A total of 2308 eyes (1154 patients) were analyzed in this study by 92 ophthalmologists. The initial version of the FAST® indicated 60% of the subjects had OSD. Rasch analysis allowed removal of some clinical signs. The LASSO method allowed elimination of some items from the original questionnaire for a 9-item and a 6-item version of FAST®. For the 6-item questionnaire, the sensitivity and specificity were 71.9% and 74.3% respectively and the area under the curve was 0.815. The FAST® questionnaire is a valid and reliable tool for use in routine clinical practice and in clinical trials. The short versions of the questionnaire allow quick detection of the majority of patients with OHT or glaucoma at risk of dry eye.

How to Monitor Disease Activity of Axial Spondyloarthritis in Clinical Practice.

Treatment guided by periodic and quantitative data assessment results in better outcomes compared to using clinical gestalt. While validated generic as well as specific disease activity measures for axial spondyloarthritis (axSpA) are available, there is vast scope to improve their actual utilization in routine clinical practice. In this review, we discuss available disease activity measures for axSpA, describe results from the survey conducted among general rheumatologists as well as Spondyloarthritis Research and Treatment Network (SPARTAN) members about disease activity measurement in daily practice, and discuss ways to improve axSpA disease activity using technological advances. We also discuss the definitions of active disease and target for the treatment of axSpA. The 2019 American College of Rheumatology (ACR)/Spondylitis Association of America (SAA)/Spondyloarthritis Research and Treatment Network (SPARTAN) axSpA treatment guidelines conditionally recommend the regular monitoring of disease activity using a validated measure such as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) or Ankylosing Spondylitis Disease Severity Index (ASDAS). Assessment of Spondyloarthritis International Society (ASAS)-European Alliance of Associations for Rheumatology (EULAR) guidelines recommend ASDAS as the most appropriate instrument for the assessment of disease activity, preferably calculated using C-reactive protein (CRP). ASAS has selected a core set of variables which were updated recently and have been endorsed by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group in order to bring homogeneity in assessment of axSpA. In a recent study, Patient-Reported Outcomes Measurement Information System (PROMIS®) measures were able to discriminate inactive, moderate, and high-very high ASDAS activity groups. A newly developed semi-objective index P4 (pain, physical function, patient global, and physician global) correlates well with BASDAI and ASDAS in axSpA and can also be used for other rheumatic diseases in busy clinical practices. Regular disease activity monitoring is critical for long-term management of axSpA and shared decision-making. The integration of electronic health records and smart devices provides a great opportunity to capture patient-reported data. Automated capture of electronic patient-reported outcome measures (ePROMs) is a highly efficient way and results in consistent regular monitoring and may improve the long-term outcomes. While currently used measures focus only on musculoskeletal symptoms of axSpA, a composite disease activity measure that can also incorporate extra-articular manifestations may provide a better assessment of disease activity.

Enhancing Patient-Reported Outcome Measures for Drug Hypersensitivity: A Validated 6-Item Quality-of-Life Questionnaire for Patients With Drug Hypersensitivity

BACKGROUNDDrug hypersensitivity reactions (DHR) can significantly impair patients’ health-related quality of life (HRQoL). However, tools for HRQoL assessment for patients with DHR are time-consuming and remain underutilized. OBJECTIVETo develop and validate an optimized version of the Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q) designed for everyday clinical use. METHODSItem response theory (IRT), a statistical framework for psychometric measurement, was used to evaluate the 15 questions from the original DrHy-Q for their respective item difficulty, discrimination, and information using prospective data from 243 patients with histories of suspected/confirmed DHR before allergy workup. Accordingly, the best-performing items were identified to develop a 6-item optimized version (DrHy-Q6), which was subsequently validated with another prospective cohort of 156 patients. RESULTSAll 15 items of the original DrHy-Q demonstrated satisfactory parameters in IRT analysis, including very high discrimination (>1.7), appropriate difficulty (in between -1.5 and 1.5) and good information (a high and broad peak in the information curve). Six items with top-ranked IRT parameters were identified to construct an optimized version, which we named the DrHy-Q6. The DrHy-Q6 demonstrated a 1-factor structure with an improved fit compared to the original DrHy-Q (comparative fit index = 0.985, Tucker–Lewis’s index = 0.974), excellent convergent validity (Unadjusted Pearson correlation with the full version = 0.955; adjusted = 0.894, p<0.001), reliability (Cronbach’s α and McDonald’s ω = 0.93), divergent validity (Pearson correlation with all Short Form 12-item Healthy Survey Version 2 [SF-12v2] subscales < 0.60, p<0.001) and discriminant validity (significantly higher scores with multiple DHR labels [42.45 ± 27.26 vs. 32.93 ± 26.66], p=0.013). CONCLUSIONSFrom an IRT perspective, the DrHy-Q and all its constituent items are psychometrically valid for HRQoL assessment. We propose an optimized 6-item version (DrHy-Q6) as an abbreviated alternative for assessing HRQoL in patients with DHR, especially for routine use in clinical practice. Patients and physicians may benefit from its streamlined length and simpler scoring algorithm.

Role of endoscopic duodenojejunal bypass liner in obesity management and glycemic control.

The treatment of obesity and its comorbidities ranges from clinical management involving lifestyle changes and medications to bariat-ric and metabolic surgery. Various endoscopic bariatric and metabolic therapies recently emerged to address an important therapeutic gap by offering a less invasive alternative to surgery that is more effective than conservative therapies. This article compre-hensively reviews the technical aspects, mechanism of action, outcomes, and future perspectives of one of the most promising endoscopic bariatric and metabolic therapies, named duodenojejunal bypass liner. The duodenojejunal bypass liner mimics the mechanism of Roux-en-Y gastric bypass by preventing food contact with the duodenum and proximal jejunum, thereby initiating a series of hormonal changes that lead to delayed gastric emptying and malabsorptive effects. These physiological changes result in significant weight loss and improved metabolic control, leading to better glycemic levels, preventing dyslipidemia and non-alcoholic fatty liver disease, and mitigating cardiovascular risk. However, concern ex-ists regarding the safety profile of this device due to the reported high rates of severe adverse events, particularly liver abscesses. Ongo-ing technical changes aiming to reduce adverse events are being evaluated in clinical trials and may provide more reliable data to sup-port its routine use in clinical practice.

Remission Depth in Metastatic Hormone-Sensitive Prostate Cancer Is Associated With Prognosis in Patients With Initial Prostate-Specific Antigen Values Above 100 Ng/ML.

Recently, new drugs have caused a paradigm shift in the treatment of metastatic hormone-sensitive prostate cancer (HSPC). Meanwhile, research has identified several prognostic factors of metastatic HSPC. The present study focused on remission depth in metastatic HSPC and evaluated its association with remission depth. We analyzed 427 patients diagnosed with metastatic HSPC with serum initial prostate-specific antigen (PSA) > 100 ng/ml. The nadir serum PSA value was used as a marker of remission depth for each duration to castration resistanceby using receiver operating characteristic (ROC) curves.Cox proportional hazards regression was used to assess for any correlation of progression-free survival (PFS) and overall survival (OS) with the nadir PSA level. The cut-off value for the nadir PSA level per time to castration resistance (TTCR) at three, five, seven, and nine years was calculated. The nadir PSA value alone was able to predict prognosis because of its high sensitivity, high specificity, and high AUC in ROC analysis. The nadir PSA level can be an independent prognostic marker not only for TTCR but also for OS on multivariate analysis. We identified the cut-off value for nadir PSA per TTCR period in patients with metastatic HSPC. The nadir PSA value alone can predict prognosis; this demonstrates utility in routine clinical practice due to its simplicity and accuracy.

557 - Tralokinumab real-world use in adults with atopic dermatitis: baseline characteristics of the first 100 patients recruited to the TRACE study in the United States

Abstract Introduction/Background Tralokinumab is a fully human, high-affinity, monoclonal antibody that specifically neutralizes interleukin-13, a key driver of atopic dermatitis (AD) pathogenesis. Numerous clinical studies have established that tralokinumab is an efficacious treatment for patients with moderate-to-severe AD, along with having a favorable safety profile. However, there is a lack of evidence on tralokinumab use in routine clinical practice, where patient management may differ from that defined by clinical trial protocols. Objectives TRACE is a global, real-world study that aims to better understand the effectiveness, safety, and clinical use of tralokinumab in patients with AD in daily practice. Methods TRACE is a global, observational, prospective, single-cohort study of tralokinumab-treated adults with moderate-to-severe AD. Overall, 11 countries across Europe, North America and the Middle East are participating. The primary objective of TRACE is to assess changes in clinical signs and symptoms of AD in patients treated with tralokinumab according to the nationally approved labels. Secondary objectives include safety, quality of life, patient-reported outcomes and treatment adherence. For this interim analysis, the objective was to report the baseline characteristics of the first 100 US patients. Results Overall, 55% of the first 100 US patients initiated on tralokinumab in the TRACE study were female; the majority (54%) were White, followed by 18% Black or African American and 12% Asian. Mean (standard deviation [SD]) age was 46.4 years (18.2) and body mass index was 28.6 kg/m2 (7.7). Patients had a mean disease duration of 13.9 years (SD 16.5), with 46% being biologic-naïve and 54% biologic-experienced. Most patients (88%) had moderate-to-severe AD, with a mean Investigator’s Global Assessment score of 3.2 (SD 0.8); mean Eczema Area and Severity Index was 15.4 (SD 7.9). A heavy symptomatic burden of disease was evident, with a mean eczema-related sleep numerical rating scale (NRS) of 4.2 (SD 3.3) and mean worst daily pruritus NRS of 6.1 (SD 2.6). Patients also reported a substantial impact of AD on quality of life; mean Dermatology Life Quality Index was 13.2 (SD 8.5). Almost one quarter (24%) of patients reported ≥1 atopic comorbidity, with asthma (12%), cardiovascular disease (8%) and autoimmune disease (6%) being the most frequent; 3% of patients had psychiatric illness. Conclusions Initial findings showed that tralokinumab is being prescribed as a first-line biologic treatment option in the US in accordance with the label. Treated patients had a heavy burden of disease with considerable impact on quality of life.

Efficacy and Safety of Low Dose Naltrexone for Chronic Pain

Naltrexone is a mu-opioid receptor antagonist increasingly used as an analgesic for chronic pain at low doses. This retrospective, observational cohort study was conducted at an academic medical center to evaluate low-dose naltrexone (LDN) efficacy and describe its use in routine clinical practice. Adults receiving LDN, doses <10 mg for ≥1 month, seen at an outpatient pain clinic from January 1, 2014 to April 1, 2022 were included. The primary outcome was change in the Pain, Enjoyment of Life, and General Activity (PEG) score after LDN. Thirty-one patients were included. Median age was 50 years and 71% were female. Median duration of pain at baseline was 5 years. Mean PEG scores were 7.27 ± 1.39 and 6.62 ± 2.04 at baseline and follow-up, respectively. Mean difference was 0.66 (95% CI [0.10–1.21], p = 0.022). Eighty-seven percent (27) of patients discontinued LDN, 52% (16) for lack of benefit, 23% (7) for loss of benefit, 10% (3) for side effects, and 3% (1) for other reasons. Seven (23%) reported side effects. LDN was associated with a statistically significant reduction in PEG in adult chronic pain patients, however the clinical significance is unclear as over 75% of patients discontinued LDN due to lack of benefit.

Vatari Guggulu, Hingvashtaka Churna, and Brihat Saindhavadya Taila in the management of rheumatoid arthritis: An open-label, prospective, single-arm multi-center study

Abstract Background: Despite significant advances in the diagnosis and treatment of rheumatoid arthritis (RA), the clinical outcomes remain unsatisfactory in a significant proportion of patients. Ayurveda management for RA (Amavata) has shown promising clinical outcomes in routine clinical practice and as per published research studies. Objective: The study was designed to assess the therapeutic effect and safety of Ayurveda interventions, Vatari Guggulu (VG), Hingvashtaka Churna (HC), and Brihat Saindhavadya Taila (BS) in the management of RA. Materials and Methods: An open-label, prospective, single-arm multicenter study was conducted at Ayurveda Research Institutes in Patna, Bhubaneswar, and Guwahati with a sample size of 180 participants. Patients of any gender aged 20–60 years with clinically diagnosed RA as per the revised American College of Rheumatology criteria and willing to provide written informed consent to participate in the study were included in the study. Ayurveda interventions, VG, HC, and BS, were administered to the study participants for 12 weeks, with a follow-up at four weeks without intervention. The primary outcome measure was a change in the Disease Activity Score-28 (DAS28) from baseline. The other outcome measures included change in the Indian Health Assessment Questionnaire Disability Index score (HAQ-DI), changes in the acute phase reactants (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), and change in the quality of life parameters (assessed through the SF-36 questionnaire). Results: A total of 180 participants were enrolled in the study, and data of 179 participants were considered for the final analysis. A statistically significant difference was observed in the outcome parameters, such as a mean change in the DAS28 score, HAQ-DI score, SF-36 score, and ESR and CRP levels (P &lt; 0.001) after 12 weeks of treatment. The mean DAS28 score changed from 6.50 ± 0.790 at baseline to 4.21 ± 1.286 on week 16 follow-up (P &lt; 0.001). No participant withdrew from the study due to adverse events. The trial interventions were well-tolerated and safe. Conclusion: The study outcomes provide preliminary evidence of the safety and potential benefits of the Ayurveda interventions in the management of RA. Further, randomized controlled studies may be planned to generate robust evidence on the therapeutic potential of these interventions so that they can be recommended for use in routine clinical practice. Trial registration: CTRI/2014/12/005242.

Comparison of Echo-Planar Imaging and Compressed Sensing in the Estimation of Flow Metrics from Aortic 4D Flow MR Imaging: A Healthy Volunteer Study.

Prolonged scanning of time-resolved 3D phase-contrast MRI (4D flow MRI) limits its routine use in clinical practice. An echo-planar imaging (EPI)-based sequence and compressed sensing can reduce the scan duration. We aimed to determine the impact of EPI for 4D flow MRI on the scan duration, image quality, and quantitative flow metrics. This was a prospective study of 15 healthy volunteers (all male, mean age 33 ± 5 years). Conventional sensitivity encoding (SENSE), EPI with SENSE (EPI), and compressed SENSE (CS) (reduction factors: 6 and 12, respectively) were scanned.Scan duration, qualitative indexes of image quality, and quantitative flow parameters of net flow volume, maximum flow velocity, wall shear stress (WSS), and energy loss (EL) in the ascending aorta were assessed. Two-dimensional phase-contrast cine MRI (2D-PC) was considered the gold standard of net flow volume and maximum flow velocity. Compared to SENSE, EPI and CS12 shortened scan durations by 71% and 73% (EPI, 4 min 39 sec; CS6, 7 min 29 sec; CS12, 4 min 14 sec; and SENSE, 15 min 51 sec). Visual image quality was significantly better for EPI than for SENSE and CS (P < 0.001). The net flow volumes obtained with SENSE, EPI, and CS12 and those obtained with 2D-PC were correlated well (r = 0.950, 0.871, and 0.850, respectively). However, the maximum velocity obtained with EPI was significantly underestimated (P < 0.010). The average WSS was significantly higher with EPI than with SENSE, CS6, and CS12 (P < 0.001, P = 0.040, and P = 0.012, respectively). The EL was significantly lower with EPI than with CS6 and CS12 (P = 0.002 and P = 0.007, respectively). EPI reduced the scan duration, improved visual image quality, and was associated with more accurate net flow volume than CS. However, the flow velocity, WSS, and EL values obtained with EPI and other sequences may not be directly comparable.

Alteraciones de la motilidad esofágica

Esophageal motility disorders (EMD) manifest clinically with the presence of dysphagia and/or chest pain related to swallowing. In order to diagnose it, it is necessary to first rule out organic causes that would explain these symptoms. In recent decades, the development of high-resolution manometry and its use in routine clinical practice has allowed for better characterization of esophageal motility disorders. The diagnostic criteria have been updated in recent years in the Chicago Classification v4.0, which establishes two large groups of motor disorders: those with esophagogastric junction outflow obstruction (EGJOO) and those with abnormal esophageal body contractility. The treatment of EMDs with EGJOO (the various presentations of achalasia and esophagogastric junction outflow obstruction) is aimed at reducing the baseline pressure in this area. Various techniques are available for this, such as pneumatic balloon dilatation, endoscopic (POEM) and surgical myotomy (Heller myotomy), and, less frequently, the use of oral drugs and botulinum toxin injection. In the case of esophageal peristalsis disorders, the goal of treatment is to control symptoms. To do so, proton pump inhibitors (PPIs) are used in patients with associated gastroesophageal reflux disease (GERD) and, in the case of disorders associated with hypercontractility, other drugs such as nitrates or calcium channel blockers and, occasionally, low-dose tricyclic antidepressants may be used.