Persistent Left Superior Vena Cava: Unanticipated Stumbling Block in Cardiac Resynchronization Therapy.

Persistent left superior vena cava (PLSVC) is a relatively rare anatomical anomaly, with a higher prevalence in those with congenital heart defects. While typically asymptomatic, its presence can complicate certain medical procedures, particularly cardiac interventions, such as the implantation of cardiac resynchronization therapy (CRT) devices, due to acute angulation. In this report, we discuss the challenges posed by the unanticipated presence of PLSVC during CRT device implantation and describe the technique used for lead placement using Judkins Right catheter for support, placing coronary wire, and later placing the left ventricle (LV) lead with the help of buddy wire technique, resulting in successful insertion of all three CRT leads despite the anatomical challenges.

Cardiac resynchronization therapy in heart failure based on Strauss criteria for left bundle branch block.

AIMS: The left bundle branch block (LBBB) is a strong predictor of response to cardiac resynchronization therapy (CRT). However, a significant number of patients do not respond to the treatment. The study sought to evaluate the impact of the stricter Strauss criteria for left bundle branch block (St-LBBB) on CRT response, hospitalizations, ventricular arrhythmia (VA) events and mortality. METHODS: This study is a retrospective analysis of prospectively collected data on heart failure (HF) patients with LBBB admitted for CRT implantation. Patients were divided into two groups according to the fulfilment or not of St-LBBB criteria. RESULTS: The study included 82 patients with ischaemic (ICM) and non-ischaemic (NICM) cardiomyopathy [46 (56%) with St-LBBB and 36 (44%) with non-St-LBBB]. Patients with St-LBBB showed higher CRT response rates compared with those with non-St-LBBB (P < 0.01), while the group with NICM exhibited the greatest benefit (P < 0.01). St-LBBB CRT responders displayed significantly lower rates of HF hospitalization (P < 0.0001) compared with the non-St-LBBB group. According to Kaplan-Meier time curves, this was primarily evident in patients with NICM (P < 0.0001). CRT responders displayed significantly fewer VA events (P < 0.001) and lower mortality rates (P < 0.0001) than non-responders. Kaplan-Meier estimates demonstrated a significantly lower incidence of VAs in NICM patients with St-LBBB (P = 0.049) compared with ICM patients with St-LBBB (P = 0.25). Lower mortality rates were observed in CRT responders than non-responders (P < 0.0001), with the group of NICM with St-LBBB criteria exhibiting the greatest benefit (P = 0.0238). CONCLUSIONS: Patients with NICM and St-LBBB present the greatest benefit concerning CRT response, HF hospitalizations, VA events and mortality. Although St-LBBB criteria seem to improve patient selection for CRT, more data are needed to elucidate the role of St-LBBB criteria in this setting.

Device-therapy in chronic heart failure: Cardiac contractility modulation versus cardiac resynchronization therapy.

AIMS: Cardiac implantable electrical devices such as cardiac resynchronization therapy with defibrillator (CRT-Ds) or cardiac contractility modulation (CCMs) are therapy options for patients with symptomatic heart failure (HF) and reduced left ventricular ejection fraction (LVEF) despite optimal medical treatment. As yet, a comparison between both devices has not been performed. METHODS AND RESULTS: The Mannheim Cardiac Resynchronization Therapy Registry (MARACANA) and the Mannheim Cardiac Contractility Modulation Observational Study (MAINTAINED) included all patients who received CRTs or CCMs in our medical centre between 2012 and 2021. For the present analysis, we retrospectively compared patients provided with either CRT-Ds (n = 220) or CCMs with additional defibrillators (n = 105) regarding New York Heart Association classification (NYHA), LVEF, tricuspid annular plane systolic excursion (TAPSE), QRS-width and other HF modification aspects after 12 months. Before implantation, CCM patients presented with lower LVEF (23.6 ± 6.2 vs. 26.3 ± 6.5%) and worse NYHA (3.03 ± 0.47 vs. 2.81 ± 0.48, both P < 0.05), compared with CRT-D patients. Follow-up improvements in NYHA (2.43 ± 0.67 vs. 2.28 ± 0.72), LVEF (30.5 ± 10.7 vs. 35.2 ± 10.5%) and TAPSE (17.2 ± 5.2 vs. 17.1 ± 4.8 to 18.9 ± 3.4 vs. 17.3 ± 3.6 mm, each P < 0.05) were comparable. The intrinsic QRS-width was stable with CCM (109.1 ± 18 vs. 111.7 ± 19.7 ms, P > 0.05), while the paced QRS-width with CRT-D after 12 months was lower than intrinsic values at baseline (157.5 ± 16.5 vs. 139.2 ± 16 ms, P < 0.05). HF hospitalizations occurred more often for CCM than CRT-D patients (45.7 vs. 16.8%/patient years, odds ratio 4.2, P < 0.001). CONCLUSIONS: Chronic heart failure patients could experience comparable 12-month improvements in functional status and ventricular reverse remodelling, with appropriately implanted CCMs and CRT-Ds. Differences in HF hospitalization rates may be due to the more advanced HF of CCM patients at implantation.

Half body irradiation (HBI) for bone metastases in the modern radiotherapy technique era - A systematic review.

Bone metastases (BMs) are the most common cause of cancer-related pain and radiation therapy plays a key role in treating pain caused by it. The half-body irradiation (HBI) is a modality that can be used to treat patients with multiple painful BMs. In the modern era, concerns about toxicity and the availability of new agents requiring robust bone marrow function have limited the use of HBI in advanced cancer. Concerns about HBI toxicity stem from outdated techniques; modern methods like volumetric modulated arc therapy (VMAT) and helical tomotherapy now allow safer irradiation of complex target volumes. We conducted a systematic review to present updated information about HBI efficacy and potential toxicity. Pain relief usually occurs very quickly 2-3 weeks after HBI. The overall pain response rate was high in all the series, accounting for a median of 84 % (75.6-89 %), with a median of 36 % complete pain response. The toxicity is usually limited to G1/G2, with very rare G3 cases. More than 50 % of patients can reduce analgesic intake after HBI. Additionally, with modern radiotherapy techniques, quality of life is improved in most patients. HBI is a safe and effective method and should once again be reconsidered for more frequent use.

Update to the study protocol: minimisation of dialysis risk in hospital patients with chronic kidney disease (MinDial): a multicentre, stepped-wedge, cluster-randomised controlled trial.

This document reports a brief update to the previously published protocol of the MinDial study.Trial registration German Clinical Trials Register DRKS00029691. Registered on 12 Sept. 2022, https://drks.de/search/en/trial/DRKS00029691 .

Right ventricular-pulmonary artery coupling in patients undergoing cardiac resynchronization therapy.

INTRODUCTION: The ratio between tricuspid annular plane systolic excursion (TAPSE) and estimated pulmonary artery systolic pressure (PASP) has been shown to be a reliable, non-invasive surrogate of the right ventricular-pulmonary artery (RV-PA) coupling. The present study analysed the association between TAPSE/PASP and response to cardiac resynchronization therapy (CRT) and the prognostic role of RV-PA in patients undergoing CRT implantation. The primary endpoints were: the association between baseline TAPSE/PASP and CRT response/cardiovascular and all-cause death. METHODS AND RESULTS: All patients having undergone CRT implantation in our Center from 2016 to 2020 were included in our retrospective analysis. The RV-PA coupling was assessed by echocardiography at baseline and 1 year follow up in CRT recipients. The cut-off value of TAPSE/PASP resulted from ROC curve analysis (i.e.<0.33 mm/mmHg). A total of 229 patients (age 69.9 ± 10.1 years; 77.7% men) were included. During a mean follow-up of 44.2 ± 17.9 months, 40 (17.5%) patients died. The baseline value of TAPSE/PASP was not significantly associated with CRT response. Patients with a more impaired TAPSE/PASP ratio had significantly worse survival rates. On multivariate Cox regression, only TAPSE/PASP ratio and estimated glomerular filtration rate were independently associated with all-cause death. Finally, the TAPSE/PASP ratio significantly increased after CRT implantation in the group of "responders" whereas it did not change in 'non-responders'. CONCLUSIONS: The baseline value of TAPSE/PASP ratio was not associated with CRT response. However, the TAPSE/PASP ratio was a strong predictor of both all-cause and cardiovascular death in CRT recipients.

Covariate-constrained randomization in cluster randomized 2 × 2 factorial trials: application to a diabetes prevention study.

BACKGROUND: Cluster randomized trials (CRTs) are randomized trials where randomization takes place at an administrative level (e.g., hospitals, clinics, or schools) rather than at the individual level. When the number of available clusters is small, researchers may not be able to rely on simple randomization to achieve balance on cluster-level covariates across treatment conditions. If these cluster-level covariates are predictive of the outcome, covariate imbalance may distort treatment effects, threaten internal validity, lead to a loss of power, and increase the variability of treatment effects. Covariate-constrained randomization (CR) is a randomization strategy designed to reduce the risk of imbalance in cluster-level covariates when performing a CRT. Existing methods for CR have been developed and evaluated for two- and multi-arm CRTs but not for factorial CRTs. METHODS: Motivated by the BEGIN study-a CRT for weight loss among patients with pre-diabetes-we develop methods for performing CR in 2 × 2 factorial cluster randomized trials with a continuous outcome and continuous cluster-level covariates. We apply our methods to the BEGIN study and use simulation to assess the performance of CR versus simple randomization for estimating treatment effects by varying the number of clusters, the degree to which clusters are associated with the outcome, the distribution of cluster level covariates, the size of the constrained randomization space, and analysis strategies. RESULTS: Compared to simple randomization of clusters, CR in the factorial setting is effective at achieving balance across cluster-level covariates between treatment conditions and provides more precise inferences. When cluster-level covariates are included in the analyses model, CR also results in greater power to detect treatment effects, but power is low compared to unadjusted analyses when the number of clusters is small. CONCLUSIONS: CR should be used instead of simple randomization when performing factorial CRTs to avoid highly imbalanced designs and to obtain more precise inferences. Except when there are a small number of clusters, cluster-level covariates should be included in the analysis model to increase power and maintain coverage and type 1 error rates at their nominal levels.

Circulating tumor cells in patients with cervical cancer undergoing chemoradiotherapy combined with brachytherapy.

Circulating tumor cells (CTCs) have significant potential to become an important tool for monitoring the effects of treatment in solid tumors. The present study reports the occurance of CTCs in cervical cancer (CC) patients during radical chemoradiotherapy (CRT), including brachytherapy (BRT), and during the follow-up period. Patients diagnosed with CC treated with radical CRT were included in the study (n=30). A total of 167 CTC-tests (MetaCell®) were provided at predefined testing time points during the study follow-up (e.g., before CRT, after CRT, every three months of follow-up). In parallel with CTC-testing, SCC-Ag were measured to compare their predictive values during treatment. CTCs were present in 96% (25/26) of patients at the time of diagnosis and in 61% (14/23) after treatment. Patients who relapsed during the 36-month follow-up (n=10) showed an elevation in pre-treatment CTC- numbers, similarly there was a significant increase in pre-treatment SCC-Ag. As next, an increased number of CTCs was observed approximately 12 weeks before relapse was diagnosed by standard imaging modalities (MRI, US, PET-CT) in 3 of 4 patients. In addition to standardized vital cytomorphology of enriched CTCs, quantitative PCR (qPCR) was used to inform the nature of CTCs before treatment. Analysis revealed increased SOX2 and POUSF expression in CTCs in the group of patients with recurrence (P < 0.02). Disease aggressiveness may be related to increased expression of stem cell markers, as found in samples from relapsed patients. CTCs may be an aid to assess tumor burden and disease aggressiveness. An increase in CTCs precedes an increase in SCC-Ag and confirmation of relapse by imaging, as shown in our study.

Is Conduction System Pacing Going to Be the New Gold Standard for Cardiac Resynchronization Therapy?

The current gold standard in device therapy for advanced heart failure (HF), which has been firmly established in HF management for more than 25 years, is classical biventricular pacing (BiV-CRT). In the last decade, a new pacing modality called conduction system pacing (CSP) has emerged as a variant for advanced cardiac device therapy. It provides pacing with preserved intrinsic cardiac activation by direct stimulation of the specific cardiac conduction system. The term CSP integrates the modalities of HIS bundle pacing (HBP) and left bundle branch area pacing (LBBAP), both of which have provided convincing data in smaller randomized and big non-randomized studies for the prevention of pacemaker-induced cardiomyopathy and for providing effective cardiac resynchronization therapy in patients with classical CRT-indication (primary approach or after failed CRT). Recent American guidelines proposed the term "cardiac physiological pacing" (CPP), which summarizes CSP including left ventricular septal pacing (LVSP), a technical variant of LBBAP together with classical BiV-CRT. The terms HOT-CRT (HIS-optimized CRT) and LOT-CRT (LBBP-optimized CRT) describe hybrid technologies that combine CSP with an additional coronary-sinus electrode, which is sometimes useful in patients with advanced HF and diffuse interventricular conduction delay. If CSP continues providing promising data that can be confirmed in big, randomized trials, it is likely to become the new gold standard for patients with an expected high percentage of pacing (>20%), possibly also for cardiac resynchronization therapy. CSP is a sophisticated new treatment option that has the potential to raise the term "cardiac resynchronization therapy" to a new level. The aim of this review is to provide basic technical, anatomical, and functional knowledge of these new pacemaker techniques in order to facilitate the understanding of the different modalities, as well as to provide an up-to-date overview of the existing randomized and non-randomized evidence, particularly in direct comparison to right ventricular and classical biventricular pacing.

A Systematic Review and Narrative Synthesis of Cognitive Training in the Treatment of Mental Illness and Substance Use Disorder.

Introduction: The one unifying and distinguishing feature of all neuropsychiatric illnesses is the co-occurrence of cognitive dysfunction. Cognitive training (CT) was developed to enhance neural connectivity and cognition and improve day-to-day functioning. However, the benefits of CT are still debated. This current systematic review aimed to examine the efficacy of CT and to identify diagnostic and CT characteristics associated with superior outcomes across a range of psychiatric disorders. Method: Studies investigating CT in psychiatric illnesses were extracted from Embase, PubMed, CINAHL, PsycINFO, and PsycARTICLES up to 17 August 2023. Inclusion criteria were randomised control trials (RCT) and English language. The primary search strategy included terms relating to cognitive training, cognitive remediation, cognitive enhancement, or cognitive rehabilitation and randomised control trials, clinical trials, or experiments. Risk of bias was assessed using RevMan Web version 8.1.1. Narrative synthesis was used to analyse findings. Due to the heterogeneity of participant demographics, diagnoses, and interventions, meta-analyses were considered inappropriate. Results: Fifteen studies, including a total of 1075 participants, were identified. Approximately 67% of studies reported significant improvements in at least one trained domain of cognitive function after CT, and 47% observed improvements in psychiatric symptoms or function. Cognitive transfer effects were not observed. Sample sizes for studies were generally small, and most CT durations were 6 weeks or less. Conclusions: Findings suggest that CT can improve cognitive function in trained domains, though little evidence of cognitive transfer effects was observed. Due to the lack of standardisation in CT format and delivery, and inadequate measures of psychiatric symptoms or daily function, there is insufficient evidence to conclude whether or not this technique may benefit cognitive impairment in psychiatric disorders, or lead to subsequent improvement in disease symptomatology. Further studies of longer duration and using consistent methodologies must be conducted to identify the benefits of CT in psychiatric disorders.

Investigating the clinical utility of global and regional myocardial work parameters in predicting response to cardiac resynchronization therapy in patients with heart failure and reduced ejection fraction.

Background: Previous studies have indicated that despite adhering to current patient selection guidelines, there remains a 30% to 40% subset of patients who do not experience improvement in heart failure (HF) after receiving cardiac resynchronization therapy (CRT). We aim to utilize echocardiographic myocardial work parameters to serve as predictors of responsiveness to CRT in patients with heart failure and reduced ejection fraction (HFrEF). Methods: We prospectively recruited patients who underwent CRT at Sun Yat-sen Memorial Hospital from June 2019 to September 2022. Comprehensive preoperative information, clinical laboratory data, conventional echocardiographic parameters and myocardial work were collected for all participants, as well as follow-up data 6 months after CRT. Results: Twenty-five patients (67.6%) showed response to CRT treatment, while twelve patients (32.4%) had no response. Compared with the non-response group, the response group had larger region constructive work [RCW: the sum of constructive work (CW) in the 9 segments of the basal, mid, and apical segments of the anterior, lateral, and posterior walls], region wasted work [RWW: the sum of wasted work (WW) in the 6 segments of the basal and mid segments of the anterior septum, posterior septum and anterior walls], and the combination of RCW and RWW (RCW + RWW) in baseline (RCW: 9,695.68±2,955.40 vs. 5,219.50±2,207.68 mmHg%, P<0.001; RWW: 3,612.08±1,723.80 vs. 1,674.33±995.23 mmHg%, P=0.001; RCW + RWW: 13,307.76±3,857.71 vs. 6,893.83±2,592.83 mmHg%, P<0.001). Furthermore, global constructive work (GCW), global wasted work (GWW), GCW + GWW, RCW, RWW, and RCW + RWW had areas under the receiver operating characteristic curve (AUCs) of 0.870, 0.770, 0.860, 0.890, 0.870, and 0.910, respectively, for predicting CRT responsiveness. Conclusions: The global and regional myocardial work parameters are associated with CRT response in CRT candidates. Particularly regional myocardial work parameters appear to be promising parameters to improve selection for CRT of patients with HFrEF.

Negligence in biomedical research: an anti-racist approach for substance use researchers.

Racism is embedded in the fabric of society at structural, disciplinary, hegemonic, and interpersonal levels, working as a mechanism that drives health disparities. In particular, stigmatized views of substance use get entangled with racialization, serving as a tool to uphold oppressive systems. While national health institutions have made commitments to dismantle these systems in the United States, anti-racism has not been integrated into biomedical research practice. The ways in which substance use researchers use and interpret race data-without engaging in structural racism as a mechanism of health inequity-can only be described as inadequate. Drawing upon concepts from the Public Health Critical Race praxis, QuantCrit, and an anti-racism research framework, we recommend a set of guidelines to help biomedical researchers conceptualize and engage with race more responsibly in substance use research.

Ineffective cardiac resynchronization pacing is associated with poor outcomes in a nationwide cohort analysis.

BACKGROUND: Delivery of cardiac resynchronization therapy (CRT) requires left ventricular myocardial capture to achieve clinical benefits. OBJECTIVE: We sought to determine whether ineffective pacing affects survival. METHODS: Ineffective ventricular pacing (VP) was defined as the difference between the percentage of delivered CRT (%VP) and the percentage of EffectivCRT in CRT devices. Using the Optum de-identified electronic health record data set and Medtronic CareLink data warehouse, we identified patients implanted with applicable devices with at least 30 days of follow-up. Kaplan-Meier and Cox proportional hazards models assessed the effect of %VP and % ineffective VP on survival. RESULTS: Among 7987 patients with 2.1 ± 1.0 years of follow-up, increasing ineffective VP was associated with decreasing survival: the highest observed survival was in the quartile with <0.08% ineffective VP and the lowest survival was in the quartile with >1.47% ineffective VP (85.1% vs 75.7% at 3 years; P < .001). As expected, patients with more than the median %VP of 97.7% had better survival than did patients with <97.7% VP (84.2% vs 77.8%; P < .001). However, patients who had >97.7% VP but >2% ineffective VP had similar survival to patients with <97.7% VP but ≤2% ineffective VP (81.6% vs 79.4%; P = .54). A multivariable Cox proportional hazards model demonstrated that <97.7% VP (adjusted hazard ratio 1.29; 95% confidence interval 1.14-1.46; P < .001) and >2% ineffective VP (hazard ratio 1.35; 95% confidence interval 1.18-1.54; P < .001) were both significantly associated with decreased survival. CONCLUSION: Ineffective VP is associated with decreased survival. In addition to maximizing the percentage of delivered CRT pacing, every effort should be made to minimize ineffective VP.

A cluster randomized trial of a rational emotive behavior therapy (REBT) program and a mindfulness-acceptance-commitment (MAC) program, with South African adolescent rugby players.

Until recently, research examining the application of Rational Emotive Behavior Therapy (REBT) in sports settings was virtually absent in South Africa. Despite the growing evidence of REBT's potential as a psychological intervention in Western nations, its use within the multicultural and sports-fervent context of South Africa remains unexplored. Moreover, limited research has addressed the impact of REBT on rugby players, with only a few case studies being reported. The current experiment employs a cluster randomized trial (CRT) to compare the effects of a 7-week preferential REBT program with a 7-week Mindfulness-Acceptance-Commitment (MAC) program on irrational beliefs, competitive anxiety and subjective performance, among adolescent South African rugby players. We also include a wait-list control group who received neither REBT nor MAC. Results indicate that athletes receiving REBT reported greater improvements in irrational beliefs, anxiety, and subjective performance, while that athletes receiving MAC also reported some improvements in anxiety. This study highlights the potential of REBT as a valuable psychological intervention in the context of South African adolescent rugby players.

Prediction of heart failure events based on physiologic sensor data in HINODE defibrillator patients.

AIMS: Hospitalizations are common in patients with heart failure and are associated with high mortality, readmission and economic burden. Detecting early signs of worsening heart failure may enable earlier intervention and reduce hospitalizations. The HeartLogic algorithm is designed to predict worsening heart failure using diagnostic data from multiple device sensors. The main objective of this analysis was to evaluate the sensitivity of the HeartLogic alert calculation in predicting worsening heart failure events (HFEs). We also evaluated the false positive alert rate (FPR) and compared the incidence of HFEs occurring in a HeartLogic alert state to those occurring out of an alert state. METHODS: The HINODE study enrolled 144 patients (81 ICD and 63 CRT-D) with device sensor data transmitted via a remote monitoring system. HeartLogic alerts were then retrospectively simulated using relevant sensor data. Clinicians and patients were blinded to calculated alerts. Reported adverse events with HF symptoms were adjudicated and classified by an independent HFE committee. Sensitivity was defined as the ratio of the number of detected usable HFEs (true positives) to the total number of usable HFEs. A false positive alert was defined as an alert with no usable HFE between the alert onset date and the alert recovery date plus 30 days. The patient follow-up period was categorized as in alert state or out of alert state. The event rate ratio was the HFE rate calculated in alert to out of alert. RESULTS: The patient cohort was 79% male and had an average age of 68 ± 12 years. This analysis yielded 244 years of follow-up data with 73 HFEs from 37 patients. A total of 311 HeartLogic alerts at the nominal threshold (16) occurred across 106 patients providing an alert rate of 1.27 alerts per patient-year. The HFE rate was 8.4 times greater while in alert compared with out of alert (1.09 vs. 0.13 events per patient-year; P < 0.001). At the nominal alert threshold, 80.8% of HFEs were detected by a HeartLogic alert [95% confidence interval (CI): 69.9%-89.1%]. The median time from first true positive alert to an adjudicated clinical HFE was 53 days. The FPR was 1.16 (95% CI: 0.98-1.38) alerts per patient-year. CONCLUSIONS: Results suggest that signs of worsening HF can be detected successfully with remote patient follow-up. The use of HeartLogic may predict periods of increased risk for HF or clinically significant events, allowing for early intervention and reduction of hospitalization in a vulnerable patient population.

Performance of the quadripolar CRT-D system: Five-year results from the Quadripolar Pacing Post-Approval Study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is associated with challenges such as elevated capture thresholds, diaphragmatic stimulation, and lead instability. OBJECTIVE: This study aimed to assess the long-term safety and efficacy of the quadripolar CRT-defibrillator (CRT-D) device system with the Quartet 1458Q left ventricular (LV) lead in a CRT-indicated population observed for 5 years and to evaluate all-cause mortality and impact of baseline characteristics on survival through 5 years. METHODS: Patients indicated for a CRT-D system were observed every 6 months after implantation for 5 years, and device performance and adverse events were assessed at each visit. The 3 primary end points were freedom from quadripolar CRT-D system-related complications through 5 years, freedom from Quartet 1458Q LV lead-related complications through 5 years, and mean programmed pacing capture threshold at 5 years. RESULTS: The study enrolled 1970 participants at 71 sites. The quadripolar CRT-D system was successfully implanted in 97.2% of participants. Freedom from quadripolar CRT-D device system-related complications through 5 years was 89.7%. Freedom from Quartet 1458Q LV lead-related complications through 5 years was 95.7%; 3.49% of participants had LV lead-related complications, and an overall LV lead complication rate was 0.0122 event per patient-year. The mean LV pacing capture threshold was 1.52 ± 1.01 V at 5 years. The 5-year survival rate was 67.4%. CONCLUSION: The quadripolar CRT-D system with the Quartet 1458Q LV lead exhibited low rates of complications and stable electrical performance through 5 years of follow-up and suggested a higher 5-year survival rate compared with traditional CRT systems.

Brain plasticity and adolescent HIV: A randomised controlled trial protocol investigating behavioural and hemodynamic responses in attention cognitive rehabilitation therapy.

Despite advances in antiretroviral pharmacology, neuroHIV in the central nervous system (CNS), causes neuronal dysregulation, which is associated with compromised neurocognition. Non-pharmaceutical interventions such as HIV cognitive rehabilitation training (HIV-CRT), have shown potential to partially reverse cognitive deficits, sequent HIV neuroinvasion. Nonetheless, no studies exist pairing cognitive outcomes with objective neuroimaging biomarkers in adolescent HIV-CRT. This longitudinal pre-post-quasi-experimental protocol examined cognitive outcomes, paired with optimal neuroimaging outcomes following customised attention training in adolescent HIV. Twenty-six adolescents living with HIV were randomly assigned to either the treatment group, which received attention CRT using ACTIVATE™, (n = 13), or to the treatment as usual group (n = 13). Cognitive outcomes were examined using the NEPSY-II, and BRIEF; whilst neuroimaging outcomes were determined by changes in oxygenated haemoglobin (HbO), as determined by functional near-infrared spectrometry (fNIRS). Functional connectivity fNIRS measures were evaluated using seed-based correlation analysis, located in the central executive network (CEN). This study serves to guide the development and identification of objective biomarkers for adolescent neuroHIV, sequent CRT amongst children living with HIV in Sub-Saharan Africa.

Association between amount of biventricular pacing and heart failure status measured by a multisensor implantable defibrillator algorithm.

Background: Achieving a high biventricular pacing percentage (BiV%) is crucial for optimizing outcomes in cardiac resynchronization therapy (CRT). The HeartLogic index, a multiparametric heart failure (HF) risk score, incorporates implantable cardioverter-defibrillator (ICD)-measured variables and has demonstrated its predictive ability for impending HF decompensation. Objective: This study aimed to investigate the relationship between daily BiV% in CRT ICD patients and their HF status, assessed using the HeartLogic algorithm. Methods: The HeartLogic algorithm was activated in 306 patients across 26 centers, with a median follow-up of 26 months (25th-75th percentile: 15-37). Results: During the follow-up period, 619 HeartLogic alerts were recorded in 186 patients. Overall, daily values associated with the best clinical status (highest first heart sound, intrathoracic impedance, patient activity; lowest combined index, third heart sound, respiration rate, night heart rate) were associated with a BiV% exceeding 99%. We identified 455 instances of BiV% dropping below 98% after consistent pacing periods. Longer episodes of reduced BiV% (hazard ratio: 2.68; 95% CI: 1.02-9.72; P = .045) and lower BiV% (hazard ratio: 3.97; 95% CI: 1.74-9.06; P=.001) were linked to a higher risk of HeartLogic alerts. BiV% drops exceeding 7 days predicted alerts with 90% sensitivity (95% CI [74%-98%]) and 55% specificity (95% CI [51%-60%]), while BiV% ≤96% predicted alerts with 74% sensitivity (95% CI [55%-88%]) and 81% specificity (95% CI [77%-85%]). Conclusion: A clear correlation was observed between reduced daily BiV% and worsening clinical conditions, as indicated by the HeartLogic index. Importantly, even minor reductions in pacing percentage and duration were associated with an increased risk of HF alerts.