Attitudes towards digital health technology for the care of people with chronic kidney disease: A technology acceptance model exploration.

BACKGROUND: Chronic Kidney Disease (CKD) is a long-term condition and a major health problem, which affects over 3.5 million adults in the UK. Use of digital technology has been proposed as a means of improving patient management. It is important to understand the factors that affect the acceptability of this technology to people living with chronic kidney disease. This study used the Technology Acceptance Model 3 (TAM) to investigate whether perceived ease of use and perceived usefulness could predict intention behaviour. It then investigated if intention to use digital technology predicted actual use. METHODOLOGY: This was a cross-sectional study whereby the TAM3 questionnaire was sent online to people known to have chronic kidney disease via Kidney Care UK. The characteristics of the respondents (age, sex, CKD stage) were recorded. PRINCIPAL FINDINGS: The questionnaire was sent to 12,399 people, of which 229 (39% drop out) completed it. The respondents' age ranged from 24-90 years and 45% (n = 102) were male. Thirty-five percent of participants had advanced kidney care, 33% (n = 76) had kidney transplant and 22% (n = 51) had CKD. A multiple regression analysis showed a perceived ease of use and perceived usefulness of the technology predicted behaviour intention to use digital health technology. Behaviour intention did not significantly predict actual use behaviour. CONCLUSION: Perceived usefulness and perceived ease of use are important factors in determining the intention of people with CKD to use digital healthcare. However, a gap exists between this intention and readiness to actually use the technology. This needs to be overcome if digital healthcare is to gain future traction in the clinical scenario.

Transvenous extraction of conduction system and lumenless pacing leads.

INTRODUCTION: Conduction system pacing (CSP), often accomplished with lumenless pacing leads, is increasingly employed to achieve physiologic ventricular activation. There are limited data on the extraction of these leads. The objective of this study was to describe the safety and efficacy of extraction of CSP pacing leads and compare outcomes with extraction of non-CSP lumenless leads. METHODS: Patients undergoing CSP/non-CSP lumenless lead removal were included. Outcomes of interest included rates of complete procedural success, complications, and successful reimplantation. RESULTS: Overall, 23 patients were included (n = 14 with CSP and n = 9 with non-CSP lumenless leads implanted in the right atrium, right ventricle, or septum). The mean age was 52.7 ± 24.0 years, 30% were female, and the mean lead age was 4.5 ± 4.4 years. The complete procedural success rate was 100%. One serious complication occurred in the non-CSP group but was unrelated to the lead of interest. Manual traction alone was successful in 57% of CSP cases (mean lead age 2.4 ± 1.7 years) and in 11% of non-CSP cases (mean lead age 7.9 ± 5.3 years). Laser sheaths were used in 43% of CSP cases and 89% of non-CSP cases; rotational cutting tools were used in no CSP cases and in 33% of non-CSP cases. Reimplantation in the conduction system was attempted with a left bundle branch pacing lead and successful in 80% (n = 4/5). CONCLUSION: Extraction of CSP and non-CSP lumenless leads is feasible with a high success rate and a good safety profile. CSP reimplantation after extraction is also feasible with good electrical performance.

SOS1 Inhibition Enhances the Efficacy of KRASG12C Inhibitors and Delays Resistance in Lung Adenocarcinoma.

The clinical effectiveness of KRASG12C inhibitors (G12Ci) is limited both by intrinsic and acquired resistance, necessitating the development of combination approaches. Here, we identified targeting proximal receptor tyrosine kinase (RTK) signaling using the SOS1 inhibitor (SOS1i) BI-3406 as a strategy to improve responses to G12Ci treatment. SOS1i enhanced the efficacy of G12Ci and limited rebound RTK/ERK signaling to overcome intrinsic/adaptive resistance, but this effect was modulated by SOS2 protein levels. G12Ci drug tolerant persister (DTP) cells showed up to a 3-fold enrichment of tumor initiating cells (TIC), suggestive of a sanctuary population of G12Ci resistant cells. SOS1i re-sensitized DTPs to G12Ci and inhibited G12C-induced TIC enrichment. Co-mutation of the tumor suppressor KEAP1 limited the clinical effectiveness of G12Ci, and KEAP1 and STK11 deletion increased TIC frequency and accelerated the development of acquired resistance to G12Ci, consistent with clinical G12Ci resistance seen with these co-mutations. Treatment with SOS1i both delayed acquired G12Ci resistance and limited the total number of resistant colonies regardless of KEAP1 and STK11 mutational status. Together, these data suggest that targeting SOS1 could be an effective strategy to both enhance G12Ci efficacy and prevent G12Ci resistance regardless of co-mutations.

Protocol for modeling acquired resistance to targeted therapeutics in adherent and suspension cancer cell lines via in situ resistance assay.

Acquired resistance to oncogene-targeted therapies is the major driver of mortality for patients with cancer. Here, we present a 6-to-16-week assay to model the development of acquired resistance in adherent and suspension cancer cell lines. We describe steps for determining therapeutic dose, assaying acquired resistance, and testing combination therapies. This protocol is a high-throughput, cost-effective, and scalable method to model acquired drug resistance to established and newly developed therapies. For complete details on the use and execution of this protocol, please refer to Sealover et al.1 and Theard et al.2.

Cardiac dysfunction in dialysing adults with end-stage kidney disease is associated with exercise intolerance: A pilot observational study.

People with end-stage kidney disease (ESKD) often exhibit impaired cardiac structure and function, which may contribute to poor exercise capacity. This study used multimodal exercise testing to investigate the central and peripheral mechanisms of exercise limitation in adults with ESKD, also comparing in-centre hemodialysis (ICHD) to home hemodialysis (HHD). Seventeen adults (55.5 ± 14.5 years; n = 14 male; n = 12 HHD) participated. Resting cardiac examinations, followed by submaximal cycling cardiopulmonary exercise testing (CPET) and functional exercise testing, revealed cardiac structural abnormalities (increased left ventricular mass) and cardiac injury. Aerobic fitness in adults with ESKD was low, with pulmonary oxygen uptake (V̇O2) at the gas exchange threshold (GET) occuring at 39 ± 8% predicted V̇O2peak. O2 pulse, an estimate of stroke volume (SV), was higher in HHD at rest (p = 0.05, ES = 0.58) and during unloaded cycling (p = 0.05, ES = 0.58) compared to ICHD. However, thoracic bioreactance derived SV at the GET was significantly higher in adults receiving ICHD versus HHD (p = 0.01, ES = 0.74). In adults with ESKD, cardiac output was positively associated with V̇O2 at the GET (r = 0.61, p = 0.04). This study highlights prevalent exercise dysfunction in adults with ESKD undergoing dialysis, with potential distinct differences between in-centre and home hemodialysis, mechanistically linked to underlying cardiac abnormalities.

Toward Tailoring Just-in-Time Adaptive Intervention Systems for Workplace Stress Reduction: Exploratory Analysis of Intervention Implementation.

BACKGROUND: Integrating stress-reduction interventions into the workplace may improve the health and well-being of employees, and there is an opportunity to leverage ubiquitous everyday work technologies to understand dynamic work contexts and facilitate stress reduction wherever work happens. Sensing-powered just-in-time adaptive intervention (JITAI) systems have the potential to adapt and deliver tailored interventions, but such adaptation requires a comprehensive analysis of contextual and individual-level variables that may influence intervention outcomes and be leveraged to drive the system's decision-making. OBJECTIVE: This study aims to identify key tailoring variables that influence momentary engagement in digital stress reduction microinterventions to inform the design of similar JITAI systems. METHODS: To inform the design of such dynamic adaptation, we analyzed data from the implementation and deployment of a system that incorporates passively sensed data across everyday work devices to send just-in-time stress reduction microinterventions in the workplace to 43 participants during a 4-week deployment. We evaluated 27 trait-based factors (ie, individual characteristics), state-based factors (ie, workplace contextual and behavioral signals and momentary stress), and intervention-related factors (ie, location and function) across 1585 system-initiated interventions. We built logistical regression models to identify the factors contributing to momentary engagement, the choice of interventions, the engagement given an intervention choice, the user rating of interventions engaged, and the stress reduction from the engagement. RESULTS: We found that women (odds ratio [OR] 0.41, 95% CI 0.21-0.77; P=.03), those with higher neuroticism (OR 0.57, 95% CI 0.39-0.81; P=.01), those with higher cognitive reappraisal skills (OR 0.69, 95% CI 0.52-0.91; P=.04), and those that chose calm interventions (OR 0.43, 95% CI 0.23-0.78; P=.03) were significantly less likely to experience stress reduction, while those with higher agreeableness (OR 1.73, 95% CI 1.10-2.76; P=.06) and those that chose prompt-based (OR 6.65, 95% CI 1.53-36.45; P=.06) or video-based (OR 5.62, 95% CI 1.12-34.10; P=.12) interventions were substantially more likely to experience stress reduction. We also found that work-related contextual signals such as higher meeting counts (OR 0.62, 95% CI 0.49-0.78; P<.001) and higher engagement skewness (OR 0.64, 95% CI 0.51-0.79; P<.001) were associated with a lower likelihood of engagement, indicating that state-based contextual factors such as being in a meeting or the time of the day may matter more for engagement than efficacy. In addition, a just-in-time intervention that was explicitly rescheduled to a later time was more likely to be engaged with (OR 1.77, 95% CI 1.32-2.38; P<.001). CONCLUSIONS: JITAI systems have the potential to integrate timely support into the workplace. On the basis of our findings, we recommend that individual, contextual, and content-based factors be incorporated into the system for tailoring as well as for monitoring ineffective engagements across subgroups and contexts.

The Effect of Different Electric Toothbrush Technologies on Interdental Plaque Removal: A Systematic Review with a Meta-Analysis.

The removal of dental plaque from the gingival margins of the teeth is essential to maintaining periodontal health. Whilst it has been established that electric toothbrushes demonstrate a greater ability to remove plaque, no systematic review has specifically investigated which technology is better for removing plaque from the interdental tooth surfaces, where plaque control may be more difficult. Three databases were searched until October 2023: MEDLINE and DOSSS via EBSCOhost and Embase. Data extraction was carried out on studies which met the inclusion criteria, and a risk of bias assessment was completed. The study findings were combined via a narrative synthesis and a meta-analysis where appropriate. A total of 77 studies were found, out of which 14 were selected and included in the analysis. The mean difference in interproximal plaque reduction, measured using the Rustogi Modified Naval Plaque Index (RMNPI) at 8 weeks, was 0.09 (p < 0.00001) in favor of the oscillating-rotating toothbrush. At 6 and 12 weeks, the mean difference in plaque reduction (RMNPI) was 0.05 (p = 0.0008) and 0.04 (p = 0.0001) in favor of the oscillating-rotating toothbrush, respectively. The studies show a tendency for oscillating-rotating toothbrushes to remove more interproximal plaque than oscillating toothbrushes, especially in a short time (8 weeks).

KSR1 regulates small-cell lung carcinoma tumor initiation and cisplatin resistance.

Small-cell lung cancer (SCLC) is designated a recalcitrant cancer due to its five-year relative survival rate of less than 7%. First line SCLC treatment has changed modestly in the last 40 years. The NeuroD1 subtype of SCLC (SCLC-N) commonly harbors MYC amplifications and other hallmarks of aggressive behavior. Finding novel therapeutic options that effectively eliminate residual disease observed after initial response to therapy is essential to improving SCLC patient outcome. Here we show that Kinase Suppressor of Ras 1 (KSR1), a molecular scaffold for the Raf/MEK/ERK signaling cascade is critical for clonogenicity and tumor initiation in vitro and in vivo in the highly aggressive, metastatic and therapy resistant NeuroD1 subtype of SCLC. Tumor-initiating cells (TICs) are reported as the sanctuary population within the bulk tumor responsible for therapeutic resistance and relapse. Previous studies concluded ERK activation was inhibitory to growth and tumor development. We show that signaling through KSR1 is conserved in SCLC-N and that it regulates tumor initiation through interaction with ERK. We further show that KSR1 mediates cisplatin resistance in SCLC-N cells. While 50% of control SCLC-N cells show resistance after 6 weeks of exposure to cisplatin, CRISPR/Cas9-mediated KSR1 knockout prevents resistance in >90% of SCLC-N cells. KSR1 KO also significantly enhances the ability of cisplatin to decrease SCLC-N TICs, indicating that targeting KSR1 might be selectively toxic to cells responsible for therapeutic resistance and tumor initiation. Thus, KSR1 function in SCLC-N serves as a novel model for understanding the role of KSR1-dependent signaling in normal and malignant tissues. These findings shed light on a key distinct protein responsible for regulation in SCLC-N tumors, and a potential subtype specific therapeutic target.

Testing a Behavioral Activation Gaming App for Depression During Pregnancy: Multimethod Pilot Study.

BACKGROUND: Depression during pregnancy is increasingly recognized as a worldwide public health problem. If untreated, there can be detrimental outcomes for the mother and child. Anxiety is also often comorbid with depression. Although effective treatments exist, most women do not receive treatment. Technology is a mechanism to increase access to and engagement in mental health services. OBJECTIVE: The Guardians is a mobile app, grounded in behavioral activation principles, which seeks to leverage mobile game mechanics and in-game rewards to encourage user engagement. This study seeks to assess app satisfaction and engagement and to explore changes in clinical symptoms of depression and anxiety among a sample of pregnant women with elevated depressive symptoms. METHODS: This multimethod pilot test consisted of a single-arm, proof-of-concept trial to examine the feasibility and acceptability of The Guardians among a pregnant sample with depression (N=18). Participation included two web-based study visits: (1) a baseline assessment to collect demographic and obstetric information and to assess clinical symptoms and (2) an exit interview to administer follow-up measures and explore user experience. Participants completed biweekly questionnaires (ie, Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7) during the trial to assess depression and anxiety symptom severity. App satisfaction was measured using 2 self-report scales (ie, Mobile Application Rating Scale and Player Experience of Needs Satisfaction scale). Engagement with The Guardians was captured using game interaction metric data. We used backward-eliminated mixed effects longitudinal models to examine the effects of app engagement and satisfaction and length of time in the study on symptoms of depression and anxiety. Content analysis was conducted on qualitative data from exit interviews. RESULTS: The 15-day and 30-day overall app retention rates were 26.6% and 15.1%, respectively. Mixed effects models found significant negative main effects of week in study (ß=-.35; t61=-3.05; P=.003), number of activities completed (ß=-.12; t61=-2.05; P=.04), days played (ß=-.12; t58=-2.9; P=.005), and satisfaction, according to the Mobile Application Rating Scale (ß=-3.05; t45=-2.19; P=.03) on depressive symptoms. We have reported about similar analyses for anxiety. There is preliminary evidence suggesting harder activities are associated with greater mood improvement than easier activities. Qualitative content analysis resulted in feedback falling under the following themes: activities, app design, engagement, fit of the app with lifestyle, perceived impact of the app on mood, and suggestions for app modifications. CONCLUSIONS: Preliminary results from this multimethod study of The Guardians indicate feasibility and acceptability among pregnant women with depression. Retention and engagement levels were more than double those of previous public mental health apps, and use of the app was associated with significant decrease in depressive symptom scores over the 10-week trial. The Guardians shows promise as an effective and scalable digital intervention to support women experiencing depression.

Does a simplified algorithm and integrated HCV care model improve linkage to care, retention, and cure among people who inject drugs? A pragmatic quality improvement randomized controlled trial protocol.

BACKGROUND: As many as 2.4 million Americans are affected by chronic Hepatitis C Virus (HCV) in the United States.In 2018, the estimated number of adults with a history of HCV infection in San Diego County was 55,354 (95% CI: 25,411-93,329). This corresponded to a seroprevalence of 2.1% (95% CI: 2.1-3.4%). One-third of infections were among PWID. Published research has demonstrated that direct-acting antivirals (DAAs) have high efficacy and can now be used by primary care providers to treat HCV. In addition, limited evidence exists to support the effectiveness of simplified algorithms in clinical trial and real-world settings. Even with expanded access to HCV treatment in primary care settings, there are still groups, especially people who inject drugs (PWID) and people experiencing homelessness, who experience treatment disparities due to access and treatment barriers. The current study extends the simplified algorithm with a streetside 'one-stop-shop' approach with integrated care (including the offer of buprenorphine prescriptions and abscess care) using a mobile clinic situated adjacent to a syringe service program serving many homeless populations. Rates of HCV treatment initiation and retention will be compared between patients offered HCV care in a mobile clinic adjacent to a syringe services program (SSP) and homeless encampment versus those who are linked to a community clinic's current practice of usual care, which includes comprehensive patient navigation. METHODS: A quasi-experimental, prospective, interventional, comparative effectiveness trial with allocation of approximately 200 patients who inject drugs and have chronic HCV to the "simplified care" pathway (intervention group) or the "usual care" pathway (control group). Block randomization will be performed with a 1:1 randomization. DISCUSSION: Previous research has demonstrated acceptable outcomes for patients treated using simplified algorithms for DAAs and point-of-care testing in mobile medical clinics; however, there are opportunities to explore how these new, innovative systems of care impact treatment initiation rates or other HCV care cascade outcomes among PWID. TRIAL REGISTRATION: We have registered our study with ClinicalTrials.gov, a resource of the United States National Library of Medicine. This database contains research studies from United States and other countries around the world. Our study has not been previously published. The ClinicalTrials.gov registration identifier is NCT04741750.

Novel molecular mechanism in Malan syndrome uncovered through genome sequencing reanalysis, exon-level Array, and RNA sequencing.

The NFIX gene encodes a DNA-binding protein belonging to the nuclear factor one (NFI) family of transcription factors. Pathogenic variants of NFIX are associated with two autosomal dominant Mendelian disorders, Malan syndrome (MIM 614753) and Marshall-Smith syndrome (MIM 602535), which are clinically distinct due to different disease-causing mechanisms. NFIX variants associated with Malan syndrome are missense variants mostly located in exon 2 encoding the N-terminal DNA binding and dimerization domain or are protein-truncating variants that trigger nonsense-mediated mRNA decay (NMD) resulting in NFIX haploinsufficiency. NFIX variants associated with Marshall-Smith syndrome are protein-truncating and are clustered between exons 6 and 10, including a recurrent Alu-mediated deletion of exons 6 and 7, which can escape NMD. The more severe phenotype of Marshall-Smith syndrome is likely due to a dominant-negative effect of these protein-truncating variants that escape NMD. Here, we report a child with clinical features of Malan syndrome who has a de novo NFIX intragenic duplication. Using genome sequencing, exon-level microarray analysis, and RNA sequencing, we show that this duplication encompasses exons 6 and 7 and leads to NFIX haploinsufficiency. To our knowledge, this is the first reported case of Malan Syndrome caused by an intragenic NFIX duplication.

Strategies to maximize lead tensile strength during extraction in three families of pacing leads.

BACKGROUND: Traction force that can be applied to an extraction rail is based on lead tensile strength, a product of its construction. A strong rail allows safe advancement of the extraction sheath. This study expands previous work providing strategies to optimize INGEVITY rail strength. OBJECTIVE: The purpose of this study was to measure forces that leads encounter in a simulated extraction procedure, determine lead response, and develop extraction recommendations for INGEVITY, INGEVITY+, and FINELINE II lead families. METHODS: Leads were positioned in a simulated right atrial appendage implant. Subsequent traction forces enabled evaluation of lead tensile strength and effectiveness of preparation/extraction techniques. RESULTS: Significant findings include (1) preserving the lead terminal pin did not decrease lead tensile strength and typically maximized it; (2) the weakest region is between the cathode and anode; (3) mid lead scar increases traction force tolerance until that scar is removed; and (4) optimal rail strength was observed using a multivenous approach with a femoral snare. Unique lead family findings include increased tensile strength of FINELINE II polyurethane vs silicone and INGEVITY active fixation vs passive fixation. CONCLUSION: This study teaches the implanting clinician there are specific extraction techniques available to improve the removal of leads that may be the best option for a patient's clinical needs. Bench testing demonstrates that lead construction drives lead behavior during an extraction. Preserving the lead terminal pin provides consistent and, in most cases, optimal rail strength. If clinically indicated, a multivenous approach using a femoral snare significantly increases rail strength and protects the vulnerable lead tip.

Clinical-radiological-pathological correlation in pulmonary arterial hypertension.

Pulmonary hypertension (PH) is defined by the presence of a mean pulmonary arterial pressure >20 mmHg. Current guidelines describe five groups of PH with shared pathophysiological and clinical features. In this paper, the first of a series covering all five PH classification groups, the clinical, radiological and pathological features of pulmonary arterial hypertension (PAH) will be reviewed. PAH may develop in the presence of associated medical conditions or a family history, following exposure to certain medications or drugs, or may be idiopathic in nature. Although all forms of PAH share common histopathological features, the presence of certain pulmonary arterial abnormalities, such as plexiform lesions, and extent of co-existing pulmonary venous involvement differs between the different subgroups. Radiological investigations are key to diagnosing the correct form of PH and a systematic approach to interpretation, especially of computed tomography, is essential.

SOS1 and KSR1 modulate MEK inhibitor responsiveness to target resistant cell populations based on PI3K and KRAS mutation status.

KRAS is the most commonly mutated oncogene. Targeted therapies have been developed against mediators of key downstream signaling pathways, predominantly components of the RAF/MEK/ERK kinase cascade. Unfortunately, single-agent efficacy of these agents is limited both by intrinsic and acquired resistance. Survival of drug-tolerant persister cells within the heterogeneous tumor population and/or acquired mutations that reactivate receptor tyrosine kinase (RTK)/RAS signaling can lead to outgrowth of tumor-initiating cells (TICs) and drive therapeutic resistance. Here, we show that targeting the key RTK/RAS pathway signaling intermediates SOS1 (Son of Sevenless 1) or KSR1 (Kinase Suppressor of RAS 1) both enhances the efficacy of, and prevents resistance to, the MEK inhibitor trametinib in KRAS-mutated lung (LUAD) and colorectal (COAD) adenocarcinoma cell lines depending on the specific mutational landscape. The SOS1 inhibitor BI-3406 enhanced the efficacy of trametinib and prevented trametinib resistance by targeting spheroid-initiating cells in KRASG12/G13-mutated LUAD and COAD cell lines that lacked PIK3CA comutations. Cell lines with KRASQ61 and/or PIK3CA mutations were insensitive to trametinib and BI-3406 combination therapy. In contrast, deletion of the RAF/MEK/ERK scaffold protein KSR1 prevented drug-induced SIC upregulation and restored trametinib sensitivity across all tested KRAS mutant cell lines in both PIK3CA-mutated and PIK3CA wild-type cancers. Our findings demonstrate that vertical inhibition of RTK/RAS signaling is an effective strategy to prevent therapeutic resistance in KRAS-mutated cancers, but therapeutic efficacy is dependent on both the specific KRAS mutant and underlying comutations. Thus, selection of optimal therapeutic combinations in KRAS-mutated cancers will require a detailed understanding of functional dependencies imposed by allele-specific KRAS mutations.

Lead Extraction and Mortality Among Patients With Cardiac Implanted Electronic Device Infection.

Importance: Complete hardware removal is a class I recommendation for cardiovascular implantable electronic device (CIED) infection, but practice patterns and outcomes remain unknown. Objective: To quantify the number of Medicare patients with CIED infections who underwent implantation from 2006 to 2019 and lead extraction from 2007 to 2019 to analyze the outcomes in these patients in a nationwide clinical practice cohort. Design, Setting, and Participants: This cohort study included fee-for-service Medicare Part D beneficiaries from January 1, 2006, to December 31, 2019, who had a de novo CIED implantation and a CIED infection more than 1 year after implantation. Data were analyzed from January 1, 2005, to December 31, 2019. Exposure: A CIED infection, defined as (1) endocarditis or infection of a device implant and (2) documented antibiotic therapy. Main Outcomes and Measures: The primary outcomes of interest were device infection, device extraction, and all-cause mortality. Time-varying multivariable Cox proportional hazards regression models were used to evaluate the association between extraction and survival. Results: Among 1 065 549 patients (median age, 78.0 years [IQR, 72.0-84.0 years]; 50.9% male), mean (SD) follow-up was 4.6 (2.9) years after implantation. There were 11 304 patients (1.1%) with CIED infection (median age, 75.0 years [IQR, 67.0-82.0 years]); 60.1% were male, and 7724 (68.3%) had diabetes. A total of 2102 patients with CIED infection (18.6%) underwent extraction within 30 days of diagnosis. Infection occurred a mean (SD) of 3.7 (2.4) years after implantation, and 1-year survival was 68.3%. There was evidence of highly selective treatment, as most patients did not have extraction within 30 days of diagnosed infection (9202 [81.4%]), while 1511 (13.4%) had extraction within 6 days of diagnosis and 591 (5.2%) had extraction between days 7 and 30. Any extraction was associated with lower mortality compared with no extraction (adjusted hazard ratio [AHR], 0.82; 95% CI, 0.74-0.90; P < .001). Extraction within 6 days was associated with even lower risk of mortality (AHR, 0.69; 95% CI, 0.61-0.78; P < .001). Conclusions and Relevance: In this study, a minority of patients with CIED infection underwent extraction. Extraction was associated with a lower risk of death compared with no extraction. The findings suggest a need to improve adherence to guideline-directed care among patients with CIED infection.

Colchicine for the Prevention of Recurrent Arrhythmia After Catheter Ablation of Atrial Fibrillation: Results of a Single-Center, Retrospective Study.

BACKGROUND: There is evidence to suggest that colchicine reduces the risk of recurrent atrial fibrillation (AF) after catheter ablation; however, the tolerability and safety of colchicine in routine practice is unknown. METHODS: Patients undergoing catheter ablation for AF who received colchicine after ablation were matched 1:1 to patients who did not by age, sex, and renal function. Recurrent AF was compared between groups categorically at 12 months and via propensity weighted Cox proportional hazards models with and without a 3-month blanking period. RESULTS: Overall, 180 patients (n = 90 colchicine and n = 90 matched controls) were followed for a median (Q1, Q3) of 10.3 (7.0, 12.0) months. Mean age was 65.3 ± 9.1 years, 33.9% were women, mean CHA2DS2-VASc score was 2.9 ± 1.5, and 51.1% had persistent AF. Most patients (70%) received colchicine 0.6 mg daily for a median of 30 days. In the colchicine group, 55 patients (61.1%) were receiving at least one known interacting medication with colchicine. After ablation, one patient required colchicine dose reduction and four patients required discontinuation. After adjusting for covariate imbalance using propensity weighting, no significant association between colchicine use and AF recurrence was identified (adjusted hazard ratio 0.94, 95% confidence interval [CI] 0.48-1.85; p = 0.853). No significant association was found between colchicine use and all-cause hospitalizations (adjusted odds ratio 0.74, 95% CI 0.28-1.96; p = 0.548). CONCLUSION: Despite the frequent presence of drug-drug interactions, a 30-day course of colchicine is well-tolerated after AF ablation; however, we did not observe any association between colchicine and lower rates of AF recurrence or hospitalization.

A phase IV, randomised, double-blind, controlled, parallel group trial to evaluate the effectiveness and safety of Balneum Plus versus emollient in the treatment of chronic kidney disease-associated pruritus in haemodialysis patients.

Background: Chronic kidney disease-associated pruritus (CKD-aP) is a common, distressing complaint in patients with advanced renal disease that is frequently overlooked. Treatment is often unsatisfactory. Balneum Plus (Almirall, Barcelona, Spain) is a cream containing 3% lauromacrogols and 5% urea, commonly used to treat atopic dermatitis. It has not been studied in CKD-aP to date. Methods: Adult haemodialysis patients were randomised 1:1 to apply Balneum Plus or E45 (Reckitt Beckiser, Slough, UK) to compare the active ingredients of lauromacrogol and urea with a control cream. Itch was defined as three episodes of itching during the last 2 weeks, appearing a few times a day, lasting a few minutes and troubling the patient [1]. Patients with other causes of itch, e.g. eczema and liver disease, were excluded. The primary outcome was a reduction in itch as measured by the visual analogue scale (VAS) score at 4 weeks and analysed using an analysis of covariance approach. Results: A total of 314 patients were screened and 58 patients were randomised, 29 in each group. Three patients dropped out in each group. The median baseline VAS scores were 6.5 [interquartile range (IQR) 4.4-8.0] in the Balneum Plus group and 6.3 (IQR 5.1-7.3) in the E45 group. After 4 weeks, VAS scores decreased to 2.6 (IQR 0.9-4.5) and 2.0 (IQR 0.5-4.8) in the Balneum Plus and E45 groups respectively (P = 0.64 for the difference). Using a validated questionnaire to assess secondary outcomes, we found that the Balneum Plus group had longer itching episodes, more difficulty staying asleep and itching was more annoying than in the E45 group. There was no significant difference in adverse events between the two groups. One patient reported inflamed spots on the abdominal skin in the Balneum Plus group. Conclusion: This is the first randomised controlled study of two different emollients for the treatment of CKD-aP and is a negative study. We found no significant difference in itch scores between Balneum Plus and E45.