Independent Committee Research Articles

Enhancing guidewire efficacy for transradial access: the EAGER randomised controlled trial

Abstract Background and Purpose The standard J tip peripheral guidewire used to perform coronary angiography was originally designed for transfemoral access and large vascular interventions over 70 years ago. The 3mm J tip on the standard wire is larger than the typical radial artery diameter and has limited ability to navigate smaller tortuous peripheral arteries increasing the risk of vessel spasm, and potentially reducing procedural success. We compared the efficacy and safety of a hydrophilic 1.5mm J tip guidewire (intervention - ‘baby J wire’) upfront versus the standard fixed core 0.035" J wire (‘control wire’). Methods Investigator initiated, blinded multicentre randomised trial conducted in Australia. Patients undergoing clinically indicated transradial coronary angiography were randomized 1:1 to either control or baby J peripheral guidewire use upfront. The primary endpoint was technical success defined as gaining access to the aortic root with the randomised guidewire. Secondary endpoints included total procedural time, time to aorta and coronary intubation, crossover rates to alternate wire or access site, fluoroscopy times, radial artery spasm, haematoma (EASY criteria), bleeding complications (BARC criteria) and vascular complications (VARC 2 criteria). Major adverse cardiac events (MACE) and clinical endpoints were adjudicated by a blinded independent clinical events committee. Results 330 patients were enrolled over a 9-month period from October 2022 to June 2023. The median age was 69 years (36% female), BMI 29kg/m2. The primary efficacy endpoint of technical success was achieved more frequently in the intervention group (96% v 85%; ARR 10.9% (95% CI 4.6 -17.2); P <0.001). Women were significantly more likely to benefit from the intervention related to higher failure rates with the control wire (69% vs 93% in men; P = < 0.001). Overall procedure times were similar between the groups (median 1135 vs 1354 seconds; P=0.094) but fluoroscopy time was lower in the baby J wire group (median 344 vs 491 seconds; P = 0.024). Radial completion of procedures was high and did not differ between groups (100% v 98%; P=0.2). Clinically significant bleeding (BARC2+) was more common in the control wire group (3% v 0%; P=0.017). There were no differences in MACE or vascular complications. Conclusion The hydrophilic 1.5mm J tip Baby J peripheral guidewire leads to greater upfront technical success and reduced fluoroscopy time for transradial coronary angiography compared to the standard 3mm J tip guidewire. The baby J hydrophilic guidewire is safe and may have key incremental benefits for the transradial approach particularly in patients with smaller diameter radial arteries including women.Primary Outcome

One-year outcomes of transcatheter mitral valve replacement in patients with severe mitral regurgitation

Abstract Background Mitral valve regurgitation (MR) is a prevalent valvular heart disease, and a subset of patients face challenges in undergoing surgical treatment. Transcatheter mitral valve replacement (TMVR) has emerged as a viable option for selected patients with severe MR deemed unsuitable for traditional valve surgery. Purpose This study aims to evaluate the feasibility, safety, durability, and clinical outcomes of a novel transapical mitral valve system (MitraFix valve) in treating moderate to severe MR patients. Methods The early feasibility study of the MitraFix TMVR transapical system is a multicenter, prospective, nonrandomized study. All patients underwent evaluation by a multidisciplinary heart team and were deemed suitable for mitral valve intervention. Clinical events were adjudicated by an independent clinical events committee. Results From June 2021 to July 2022, 10 patients (mean age: 71.2 ± 7.4 years, 40% male) were enrolled. The mean Society of Thoracic Surgeons(STS) predicted risk of mortality was 7.5 ± 2.7%. All implants were successful, with a mean operational time of 45.2 ± 25.9 min. One patient was converted to open cardiac surgery after successfully implanting the valve due to persistent apical bleeding. At 1-year follow-up, all-cause mortality was 20%, with a cardiovascular mortality at 10.0%. Among survival patients, 87.5% of surviving patients had MR ≤1+ and 75% patients were in NYHA functional class I or II at 1 year. The overall KCCQ score significantly increased from 55.8 (42.9, 72.9) points at baseline to 77.5 (73.7, 88.6) points at 1-year follow up (P = 0.012). Left ventricular ejection fraction showed no significant change from basline (51.5%) to 1 year (50.0%) (P=0.799). No evidence of mitral stenosis or left ventricular outflow tract (LVOT) obstruction was observed. Conclusions The MitraFix TMVR transapical system demonstrated excellent valve function, low mortality, sustained MR elimination and clinical improvement up to one year in this study. Further studies, encompassing a larger cohort of patients and an extended follow-up duration, are needed to confirm these findings.Change in MR and NYHA functional classChange in Quality-of-Life Assessment

Multi-modal artificial intelligence-based prediction for cardiovascular mortality after transcatheter aortic valve implantation: a time-to-event survival prediction

Abstract Background Predicting long-term outcomes following Transcatheter Aortic Valve Implantation (TAVI) presents a significant challenge. Objective We aimed to predict post-TAVI long-term cardiovascular mortality using multimodal data and employing time-to-event artificial intelligence (AI) algorithms. Methods This study enrolled 3,973 consecutive patients from the prospective TAVI registry (between August 2007 and June 2023). Multimodal information was collected and extracted as numerical data for each patient, encompassing clinical history, medication, laboratory, procedural characteristics, ECG, angiography, echocardiography (TTE and TEE), and CT. Clinical outcomes were adjudicated by an independent clinical event committee. From the multimodal information, 147 features were extracted at baseline before the TAVI procedure. The datasets were divided into a training/validation set (80%) and a hold-out test set (20%) for model development and evaluation, respectively. Cox-LASSO feature selection was employed to identify the most relevant features, followed by the implementation of Random Survival Forest (RSF), Gradient Boosting Survival Analysis (GBSA), and Survival Support Vector Machine (SSVM) to predict the timing and occurrence of cardiac death events in patients. Feature selection, model parameters, and hyperparameters selection were performed using 10-fold cross-validation on the training set. Model performance was evaluated using different metrics, such as the concordance index (c-index) and cumulative Area Under the Curve (C-AUC) on a 20% untouched test set. Results In the patient cohort, 28.4% experienced cardiovascular death. Features were selected from various modalities, including 22 from clinical history, two from medication, eight from laboratory tests, one from ECG, eight from CT scans, and five from echocardiography and angiography. In the univariate Cox-PH model, all features exhibited a C-index ranging from 0.50 to 0.57. In the test set, the conventional Multivariate Cox-PH model achieves a c-index of 0.59 (C-AUC: 0.56). RSF, GBSA, and SSVM achieve a C-index of 0.70 (C-AUC: 0.69), 0.66 (C-AUC: 0.64), and 0.69 (C-AUC: 0.68), respectively, in the holdout test set. Conclusion Integrating multimodal information, encompassing imaging, signal, laboratory data, and clinical history, with AI algorithms has markedly enhanced the prediction of long-term cardiac outcomes following the TAVI procedure. The initially developed model can predict the probability of cardiac death up to 10 years. Furthermore, the RFS model significantly outperformed the conventional Cox model in predicting time-to-event outcomes.

Mechanisms leading to peri-procedural myocardial infarction in patients with focal versus diffuse coronary artery disease

Abstract Background PMI are characterized by an elevation in cardiac biomarkers, such as troponin, following PCI. Adherence to the 4th UDMIof PMI necessitates not only elevated cardiac biomarkers but also the presence of ECG changes, new loss of viable myocardium, or angiographic findings indicative of a procedural complication. Understanding the mechanisms underlying PMI and their associated factors is of paramount clinical significance. Our goal was to investigate the specific pathways contributing to the occurrence of PMI in stable patients undergoing PCI. Methods This prospective study was performed at 23 sites and enrolled patients with at least one epicardial lesion with an FFR≤0.80 planned to be treated by PCI. Each patient underwent a standardized physiological protocol, including manual FFR pullbacks with PPG calculation for the characterization of CAD patterns. The median PPG value (0.62) was used to divide patients into predominantly focal or diffuse disease. Troponin levels were measured after PCI, and patients exhibiting an elevation exceeding 5 times the upper limit of normal (ULN) were subject to evaluation by an independent clinical events committee. In addition, patients with large troponin elevation (>70 times above the ULN) were adjudicated as PMI as a standalone criterion. The primary objective was to investigate the mechanism leading to PMI in patients with focal versus diffuse CAD. Results Overall, 855 patients were included in this analysis, with 34.5% (295 patients) exhibiting a troponin elevation exceeding 5 times the ULN. Among these cases, 66 (7.7%) were adjudicated as PMI. The prevalence of secondary criteria for PMI was as follows: ECG changes at 7.6% (5/66), new loss of viable myocardium at 0%, side branch occlusion at 18.2% (12/66), and large troponin elevation at 84.8% (56/66). Diffuse disease (PPG < 0.62) was significantly associated with PMI (OR 1.71, 95% CI 1.03 to 2.88, p-value = 0.038). In the overall population, the occurrence of ECG changes after PCI was 0.7% in focal disease compared to 0.8% in diffuse disease (p-value=1.0). Side branch occlusion after PCI was observed in 0.7% in focal disease vs. 2.5% in diffuse disease (p-value=0.04), and large troponin elevation occurred in 4.8% in focal disease vs. 8.5% in diffuse disease (p-value=0.03). Additionally, PPG was significantly associated with the incidence of side branch occlusion (OR 1.71, 95% CI 1.03 to 2.88, p-value=0.038) and large troponin elevation after PCI (OR 1.83, 95% CI 1.06 to 3.22, p-value=0.038). Conclusion The presence of diffuse atherosclerosis, as defined by PPG, was linked to an increased risk of PMI. The mechanisms leading to PMI differed between patients with focal and diffuse disease. Patients with diffuse disease demonstrated a higher incidence of branch occlusion and large troponin elevation following PCI compared to those with focal CAD. Targeting patients with high PPG may improve outcomes after PCI.MACE by PPG

One-year clinical outcome of aspirin-free prasugrel monotherapy following stent implantation in patients with chronic coronary syndrome: insight from ASET-JAPAN study

Abstract Background Single antiplatelet therapy with a potent P2Y12 inhibitor without aspirin after coronary stent implantation may provide an adequate balance between ischemic and bleeding risks in selected patients. The 3-month follow-up of the Acetyl-Salicylic Elimination Trial (ASET)-Japan pilot study demonstrated the feasibility and safety of Prasugrel monotherapy without aspirin after successful percutaneous coronary intervention (PCI) in selected patients with chronic coronary syndrome (CCS). Purpose The current study aimed to evaluate the 1-year clinical outcome in the ASET-Japan. Methods The ASET-Japan pilot study was designed to demonstrate the feasibility and safety of the approved dose of prasugrel monotherapy in Japan without aspirin after optimal PCI with a platinum-chromium everolimus-eluting stent in CCS population. After successful procedure, all patients were treated with a locally approved maintenance dose of 3.75 mg/day of Prasugrel monotherapy up to 3-month. After 3-month, the choice of antiplatelet therapy was left to the discretion of the investigators. Patients were followed up to 1 year. The target lesion-related endpoint was a composite of cardiac death, spontaneous target-vessel myocardial infarction (MI) >48 h after the index PCI or clinical-driven target lesion revascularisation. Patient-Oriented Composite Endpoint (POCE) was defined as a composite of all cause mortality, any stroke, any MI and any revascularisation. Spontaneous MI was defined according to Forth universal definition. The event rate was estimated by the Kaplan-Meier method. The event was adjudicated by an independent clinical event committee. Results A total of 208 patients were enrolled in the study. The average anatomical SYNTAX score was 7.96 (±4.6). After procedure, prasugrel monotherapy was immediately initiated. After 3-month, Prasugrel monotherapy was continued in 88.6% up to 1-year. Aspirin monotherapy was prescribed to 10 patients (5.0%), while 6 patients (3.0%) were on DAPT at 1-year. All-cause mortality rate was 1.49%, with no occurrence of cardiovascular death. Revascularisation occurred in 4.0% (n=8) with no occurrence of TLR, while one patient (0.5%) underwent a clinical driven target vessel revascularisation. In summary, 7 out of 8 revascularisations were non-target vessel revascularisation (6 clinically-driven non-TVR). Spontaneous non TV-MI occured in 0.5% (n=1) of patients. There was no definite/probable stent thrombosis up to 1 year. The target lesion related endpoint rate at 1-year was 0%, whereas 1-year POCE rate was 7.0% (n=14). Conclusion Discontinuation of Aspirin and Prasugrel monotherapy at a low maintenance dose of 3.75 mg/day following an angiographically successful stent deployment was feasible and safe in selected patients with CCS and low SYNTAX score. This safety profile is confirmed at 1 year while the investigators, in their large majority and at their own discretion, had maintained the prasugrel treatment.

Suicide in young and middle-aged individuals: lessons from a psychosocial autopsy study

Abstract Background Sociodemographic characteristics of suicides are available from Statistics Netherlands. To improve suicide prevention, it is not only necessary to know who dies but also why people die. A psychosocial autopsy was conducted in the Netherlands to investigate differences in psychosocial characteristics and precipitating factors of suicides of young (<30) and middle-aged (40-70) suicide decedents. Methods Data were collected from bereaved individuals. A questionnaire detailed sociodemographic and psychosocial characteristics of the decedents. We reconstructed the suicidal process in the months preceding the suicide in an interview. Findings from the questionnaire and interview were integrated. An independent expert committee formulated recommendations for suicide prevention. Results 162 suicides were investigated. Young decedents showed high levels of substance use and academic pressure. Young adults with developmental disorders were vulnerable in the transition to adulthood. Young males reached out less to support and care. By contrast, suicides of young females were distinguished by comorbidity of psychiatric disorders, frequent suicidal behaviours, high levels of care use, wait lists and a loss of (treatment) perspective, harmful social media use and bullying. Work and financial problems were common in middle-aged decedents. Physical disability and pain were frequently mentioned for middle-aged females. Suicide in middle-aged males was characterized by financial distress, interpersonal conflicts such as divorce, high levels of binge drinking and addiction. Conclusions Our data provide a topology of the needs of individuals at risk for suicide. Suicide prevention strategies can be improved by better transition support and explicit suicide monitoring in young adults with a developmental disorder, active waitlist policies in mental healthcare, and improved collaboration between debt counsellors and mental care professionals based on shared accountability. Key messages • Bereaved individuals elucidated a wide range of psychosocial problems in suicide decedents. • Suicide prevention should adhere to a needs-based approach.

Influence of pathophysiological patterns of coronary artery disease on the safety and efficacy of percutaneous coronary intervention

Abstract Background Impaired blood flow after PCI, reflected by low FFR, portends a worse prognosis. Prior to intervention, pressure gradient distributions offer insights into the likelihood of subsequent PCI success. The pullback pressure gradient (PPG) serves as a quantifiable measure of CAD patterns: values approximating 1 signify focal disease, while values approaching 0 suggest diffuse disease. This study aimed to assess the impact of pathophysiological CAD patterns on the safety and efficacy of PCI. Methods PPG Global was a prospective, investigator-initiated, multicenter study, single-arm that enrolled patients with at least one lesion with an FFR ≤ 0.80 scheduled to be treated by PCI. The study enrolled 1004 patients (1057 vessels). A standardised physiological assessment was performed, including online PPG calculation from manual FFR pullbacks. CAD patterns were defined as predominantly focal or diffuse disease based on the median PPG value. The study was powered to ascertain the predictive capacity of PPG for optimal PCI results (defined as FFR≥0.88 after PCI) as assessed by the AUC. Immediate PCI outcomes were assessed using post-PCI FFR and CFR. Following PCI, biomarkers (troponin) were collected. An independent clinical events committee adjudicated periprocedural myocardial infarction. The assessment of peri-procedural myocardial infarction (MI) adhered to the criteria outlined in the 4th Universal Definition of Myocardial Infarction. Target vessel failure (TVF) was defined as cardiac death, myocardial infarction and target vessel revascularisation. Results One thousand and four patients with 1057 vessels were included. The mean FFR was 0.68 ± 0.12, PPG 0.62 ± 0.17, post-PCI FFR 0.87 ± 0.07, and post-PCI CFR was 3.19 ± 1.93. PPG was significantly correlated with the change in FFR after PCI (r=0.65, 95% CI: 0.61-0.69, p<0.001) and showed an area under the curve of 0.82 (95% CI: 0.79-0.84) to predict optimal revascularisation. Suboptimal FFR (<0.88) after an angiographically successful PCI occurred in 471 vessels (53.5%) and was significantly higher in patients with diffuse disease (37.1% vs 74.0%, p<0.001). The change in CFR was sixfold higher in patients with high PPG (delta CFR focal 1.18 ± 1.94 and diffuse 0.19 ± 1.52, p<0.001). The rate of in-hospital TVF was similar between patients with focal vs diffuse disease (5.1% vs 8.5%, p=0.060). The incidence of periprocedural MI was significantly higher in patients with diffuse disease (5.9% vs 9.8%, p=0.050; OR 1.83, 95% CI 1.02 to 3.34). Conclusions Pathophysiological CAD patterns distinctly affect the safety and efficacy of PCI. PCI in focal disease was associated with improved physiological outcomes and a lower rate of periprocedural myocardial infarction compared to diffuse disease. Quantifying PPG before intervention reliably predicted post-PCI FFR. Further investigation through a randomised trial is warranted to explore the potential advantages of a PPG-guided PCI strategy.PPG and Revascularisation OutcomesPPG and FFR correlation Pre and Post-PCI

HIV DNA Levels in Persons Who Acquired HIV in the Setting of Long-Acting Cabotegravir for HIV Prevention: Analysis of Cases from HPTN 083 and 084.

We evaluated HIV DNA levels in individuals who received long-acting cabotegravir (CAB-LA) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis in the HPTN 083 and 084 trials and had HIV DNA testing performed to help determine HIV status. HIV DNA testing was performed using peripheral blood mononuclear cell (PBMC) samples collected after a reactive HIV test was obtained at a study site. DNA was quantified using droplet digital PCR (lower limit of detection [LLOD]: 4.09 copies/million PBMCs). Final HIV status and the timing of the first HIV-positive visit were determined by an independent adjudication committee based on HIV test results from real-time site testing and retrospective testing at a centralized laboratory. HIV DNA testing was performed for 133 participants [21 HIV-positive (7 CAB-LA arm, 14 TDF/FTC arm) and 112 HIV-negative; 1-6 tests/person]. For persons with HIV, the time between the first HIV-positive visit and collection of the first sample for DNA testing was a median of 81 days for those receiving CAB-LA (range 41-246) and 11 days for those receiving TDF/FTC (range 3-127). Four (57.1%) of the seven CAB-LA cases with infection had a low initial DNA result [three detected <LLOD; one near the LLOD (4.2 copies/106 PBMCs); in 2/4 cases, the DNA level was still <10 copies/106 PBMCs ≥40 weeks after the first HIV-positive visit. In contrast, only 3/14 (21.4%) of the TDF/FTC cases had a low or negative initial DNA test result (one not detected; two <10 copies/106 PBMCs). In this study, the time between the first HIV-positive visit and the first DNA test was longer in the CAB-LA cases than the TDF/FTC cases. Despite this difference, low or undetectable DNA levels were more frequently observed in the CAB-LA cases. This suggests that CAB-LA exposure may limit seeding of the HIV reservoir in early infection.

Enhancing Financial Reporting Quality: The Influence of Audit Committee Attributes and the Role of Audit Quality

This study to analyze the influence of the positive Characteristics of the audit committee consisting of an independent audit committee, knowledge accountancy audit committee, number meeting audit committee, and size audit committee on quality reporting finance. Besides that For analyzing audit quality strengthening moderation between characteristics of the audit committee with quality reporting finance. Research This uses agency theory which emphasizes the conflict of interest between the principal and agent. Research This is a study associative with using secondary data from the Indonesia Stock Exchange (BEI) or via the company website of each sample. The sample collection technique sample uses method purposive sampling. Sample in study This is all over incoming companies The LQ 45 index is listed on the Indonesia Stock Exchange (IDX) with a total sample of 120 observations. For the test, the hypothesis used MRA analysis with the use of application data. The results of the research include the independent audit committee, knowledgeaccountancy audit committee, number meeting audit committee, and the number of influential audit committees for quality reporting finance. Companies that use Big Four auditors can strengthen the connection between the independent audit committee and knowledge accountancy audit committee on quality reporting finance whereas companies that use Big 4 auditors weaken the connection amount meeting audit committee and the amount audit committee on quality reporting finance.

Efficacy of High Flow Nasal Cannula in the Treatment of Patients with COVID-19 with Acute Respiratory Distress Syndrome: Results of Single Centre Study in Vietnam.

Most hospitalized patients required invasive or non-invasive ventilation and High Flow Nasal Cannula (HFNC). Therefore, this study was conducted to describe the characteristics of patients with severe Coronavirus Disease-2019 (COVID-19) treated by HFNC and its effectiveness for reducing the rate of intubated-mechanical ventilation in the Intensive Care Unit (ICU) of Phu Chanh COVID-19 Department-Binh Duong General Hospital. It was a cross-sectional and descriptive study. All severe patients with COVID-19 with acute respiratory failure eligible for the study were included. Patient characteristics, clinical symptoms, laboratory results, and treatment methods were collected for analysis; parameters and data related to HFNC treatment and follow-up were analysed. 80 patients, aged of 49.7 ± 16.6years, were treated with HFNC at admission in ICU. 14 patients had type 2 diabetes (17.5%), 3 patients had chronic respiratory disease (3.8%), 19 patients had high blood pressure (23.8%), and 5 patients with other comorbidities (7.4%). The majority of patients with severe COVID-19 had typical symptoms of COVID-19 such as shortness of breath (97.5%), intensive tired (81.3%), cough (73.7%), anosmia (48.3%), ageusia (41.3%), and fever (26.3%). The results of arterial blood gases demonstrated severe hypoxia under optimal conventional oxygen therapy (PaO2 = 52.5 ± 17.4mmHg). Respiratory rate, SpO2, PaO2 were significantly improved after using HFNC at 1st day, 3rd day and 7th day (P < 0.05; P < 0.05; P < 0.01; respectively). Receiver operating characteristics (ROC) index was significantly increased after treating with HFNC vs before HFNC treatment (4.79 ± 1.86, 5.53 ± 2.39, and 7.41 ± 4.24 vs 2.97 ± 0.39; P < 0.05, P < 0.05 and P < 0.01, respectively). 54 (67.5%) patients were success with HFNC treatment and 26 (32.5%) patients with HFNC failure needed to treat with Continuous Positive Airway Pressure (CPAP) (13 patients; 50%) or intubated ventilation (13 patients; 50%). HFNC therapy could be considered as a useful and effective alternative treatment for patients with acute respiratory failure. HFNC might help to delay the intubated ventilation for patients with respiratory failure and to minimise the risk of invasive ventilation complications and mortality. However, it is crucial to closely monitor the evolution of patient's respiratory status and responsiveness of HFNC treatment to avoid unintended delay of intubation-mechanical ventilation. An independent ethics committee approved the study (The Ethics Committee of Binh Duong General Hospital; No. HDDD-BVDK BINH DUONG 9.2021), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice.

Financial Resource Availability and Implementation of Child Protection and Safeguarding Programs in Kwale County, Kenya

The Kenya child protection data on Kwale County revealed an increase of child negligence cases from 49.6% in 2020-2021 to 61.7% in 2022-2023. This has led to the establishment of various child protection and safeguarding programs to curb child protection and safeguarding menace in the county. Despite this effort, implementing such child protection and safeguarding programs has experienced problems. Thus the purpose of this study was to establish the influence of financial resource availability in the implementation of Child Protection and Safeguarding Programs in Kwale County, Kenya .The research was grounded in complexity theory and implementation theory. A descriptive research approach was employed to accurately depict the target population, which included key program personnel such as social workers, government officials, and child/probation officers involved in child protection programs in Kwale County. The sampling frame encompassed personnel from 11 NGOs, 2 government agencies, and 3 rescue centers currently implementing child protection programs in the county. Proportionate and simple random sampling were used for the NGOs and CBOs, while census sampling was employed for the government agencies and rescue centers. Of the 141 selected participants for the sample, 132 responded to the open and closed-ended questionnaires. Quantitative data was analyzed using SPSS, including descriptive statistics (frequencies, percentages, means, and standard deviations) and inferential statistics (correlation and multiple linear regression).Correlation analysis revealed that a financial resource availability showed a correlation of (r=0.859, p=0.000). Multiple linear regression indicated financial resource availability had a significant positive impact (B=0.351, p=0.00).To enhance child protection programs in Kwale County, the study recommends that organizations diversify funding sources, Implement clear reporting mechanisms and independent oversight committees can enhance transparency and accountability. Long-term financial planning, including emergency funds and scenario planning, along with stakeholder engagement, will help create a stable financial environment for implementing child protection and safeguarding programs in Kwale County.

Blood pressure targets for hypertension in people with chronic renal disease.

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease, development of end-stage renal disease, and all-cause mortality. It affects around 10% of the population worldwide. The prevalence of hypertension in people with CKD ranges from 22% in stage 1 to 80% in stage 4. Elevated arterial blood pressure is one of the major independent risk factors for adverse cardiovascular events. Thereby, reducing blood pressure to below standard targets may be beneficial but could also increase the risk of adverse events. The optimal blood pressure target in people with hypertension and CKD remains unknown. Primary: to compare the effects of standard and lower-than-standard blood pressure targets for hypertension in people with chronic kidney disease on mortality and morbidity outcomes. Secondary: to assess the magnitude of reductions in systolic and diastolic blood pressure, the proportion of participants reaching blood pressure targets, and the number of drugs necessary to achieve the assigned target. We used standard, extensive Cochrane search methods. We searched the Cochrane Hypertension Specialized Register, CENTRAL, MEDLINE, Embase, one other database, and two trial registers up to 8 February 2023. We also contacted authors of relevant papers regarding further published and unpublished work. We applied no language restrictions. We included randomized controlled trials (RCTs) in people with hypertension and CKD that provided at least twelve months' follow-up. Eligible interventions compared lower targets for systolic/diastolic blood pressure (130/80 mmHg or lower) to standard targets for blood pressure (140 to 160/90 to 100 mmHg or lower). Participants were adults with CKD and elevated blood pressure documented in a standard way on at least two occasions, or already receiving treatment for elevated blood pressure. We used standard Cochrane methods. Our critical outcomes were: total mortality, total serious adverse events, total cardiovascular events, cardiovascular mortality, and progression to end-stage renal disease. Important outcomes were: participant withdrawals due to adverse effects, and number of participants with a doubling of serum creatinine level or at least a 50% reduction in the glomerular filtration rate (GFR) at the end of the study. We used GRADE to assess the certainty of the evidence for the critical outcomes. This review received no funding. We included six RCTs that contributed data for meta-analysis, involving 7348 participants overall (range 840 to 4733 people per study). The mean follow-up was 3.6 years (range 1.0 to 8.0 years). Three studies were publicly funded, two were privately funded, and one had both public and private funding. All RCTs provided individual participant data. None of the included studies blinded participants or clinicians because of the need to titrate antihypertensive drugs to reach a specific blood pressure target. However, an independent committee blinded to group allocation assessed clinical events in all studies. Critical outcomes. Compared with standard blood pressure targets, lower targets likely result in little to no difference in total mortality (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.76 to 1.06; 6 studies, 7348 participants), total serious adverse events (RR 1.01, 95% CI 0.94 to 1.08; 6 studies, 7348 participants), and total cardiovascular events (RR 1.00, 95% CI 0.87 to 1.15; 5 studies, 6508 participants), all with moderate-certainty evidence. Compared with standard blood pressure targets, lower targets may result in little to no difference in cardiovascular mortality (RR 0.90, 95% CI 0.70 to 1.16; 6 studies, 7348 participants) and progression to end-stage renal disease (RR 0.94, 95% CI 0.80 to 1.11; 4 studies, 4788 participants), both with low-certainty evidence. Important outcomes. We found little to no differences in: participant withdrawals due to adverse effects; and the number of participants with a doubling of serum creatinine level, or at least a 50% reduction in GFR at the end of the study. Exploratory outcomes. Compared to the standard blood pressure target groups, participants in the lower target groups achieved lower systolic and diastolic blood pressure values after one year, and required a higher number of antihypertensive drugs at the end of the studies. A higher proportion of participants in the standard blood pressure target groups achieved the targets they were assigned than did participants in the intensive target groups. Compared to a standard blood pressure target, lower blood pressure targets probably result in little to no difference in total mortality, total serious adverse events, and total cardiovascular events, and may result in little to no difference in total cardiovascular mortality or in the progression to end-stage renal disease in people with hypertension and CKD. However, the evidence underpinning these conclusions has several limitations. All studies were open design, blood pressure measurement was performed at a medical office, and there was scant information about adverse events. Future research should include high-quality adverse event data, report results for people with different levels of proteinuria, and consider out-of-office blood pressure monitoring. Several studies are ongoing, and may provide new evidence for this topic in the near future.

Implementation and validation of face de-identification (de-facing) in ADNI4.

Recent technological advances have increased the risk that de-identified brain images could be re-identified from face imagery. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a leading source of publicly available de-identified brain imaging, who quickly acted to protect participants' privacy. An independent expert committee evaluated 11 face-deidentification ("de-facing") methods and selected four for formal testing. Effects of de-facing on brain measurements were comparable across methods and sufficiently small to recommend de-facing in ADNI. The committee ultimately recommended mri_reface for advantages in reliability, and for some practical considerations. ADNI leadership approved the committee's recommendation, beginning in ADNI4. ADNI4 de-faces all applicable brain images before subsequent pre-processing, analyses, and public release. Trained analysts inspect de-faced images to confirm complete face removal and complete non-modification of brain. This paper details the history of the algorithm selection process and extensive validation, then describes the production workflows for de-facing in ADNI. ADNI is implementing "de-facing" of MRI and PET beginning in ADNI4. "De-facing" alters face imagery in brain images to help protect privacy. Four algorithms were extensively compared for ADNI and mri_reface was chosen. Validation confirms mri_reface is robust and effective for ADNI sequences. Validation confirms mri_reface negligibly affects ADNI brain measurements.

A-021 Evaluation of a Novel N Terminal Pro B Type Natriuretic Peptide Assay as an aid in the Diagnosis of Acute Heart Failure in the Emergency Department

Abstract Background The signs and symptoms of acute heart failure (AHF) may overlap with other conditions and lead to diagnostic difficulty in the undifferentiated patient with dyspnea. The particularly high negative predictive value (NPV) of natriuretic peptides (NPs) in excluding AHF have rendered these assays especially useful in evaluating dyspnea in acute care setting. This study was conducted to assess the diagnostic performance of a novel N-terminal pro-B type natriuretic peptide (NT-proBNP) assay in the intended use patient population in the emergency department (ED). Methods A multicenter study was conducted in the U.S. on individuals presenting to the ED with dyspnea and a suspicion of AHF. Blood specimens were collected and tested using the Beckman Coulter Access NT-proBNP assay on the DxI 9000 Immunoassay Analyzer. Test results were compared to an adjudicated diagnosis clinical endpoint performed by an independent Clinical Events Committee blinded to the Access NT-proBNP result. Performance included NPV and sensitivity of an age-independent cut point of &amp;lt;300 ng/L to exclude AHF, and the positive predictive value (PPV) of the age-dependent cut points of &amp;gt;450, &amp;gt;900, and &amp;gt;1800 ng/L for ages &amp;lt;50 years, 50-75 years, and &amp;gt;75 years, respectively, for the diagnosis of AHF. The sample size required to achieve a 95% two tailed confidence interval (CI) was 150 subjects per age group to provide clinical performance at 90% (±10%) sensitivity. Sample size was based upon CLSI EP24-A2, Assessment of the Diagnostic Accuracy of Laboratory Tests Using Receiver Operating Characteristic Curves. Sensitivity and specificity were calculated at a series of cutoff points and plotted in separate receiver operation curves (ROC) for an overall age-independent rule-out analysis and for individual age-dependent groups separately. Area under the receiver operator characteristic curve (AUROC) was reported with 95% 2-sided CI. NPV and PPV with respective 95% 2-sided score CI was computed for the overall age-independent cut point and for each age group cohort. Results Of 490 enrolled patients, 41% were adjudicated with AHF with a median (Q1, Q3) age of 60 (47-76) years, and distributions of 46.1% female, 60.8% White and 38.2% Black. The assay had an AUROC for AHF of 0.88 (P&amp;lt;0.001), comparable to other commercially available NT-proBNP assays. The rule-out cut point of &amp;lt;300 ng/L had 96% sensitivity and NPV of 95%. Age-dependent cut points had sensitivity of 84%, 90%, and 87%, specificity of 81%, 70% and 61%, and PPV of 72%, 62%, and 74%, respectively. Conclusions The Access NT-proBNP assay demonstrated high clinical performance in the diagnosis and exclusion of acute HF in the undifferentiated dyspneic patient population and performed similarly well to validated assays used in current clinical practice. Given the continued increase in importance and reach of natriuretic peptide testing, these results are useful to extend availability of this assay to a larger audience.

Unravelling the Causal Relationship between Endometriosis and the Risk for Developing Venous Thromboembolism: A Pooled Analysis.

To investigate the effect of endometriosis on venous thromboembolism (VTE) in oral contraceptive (OC) users. Pooled analysis on a harmonized dataset compromising international patient-centric cohort studies: INAS-VIPOS, INAS-SCORE, and INAS-FOCUS. Eleven European countries, the United States, and Canada. Individuals being newly prescribed an OC with or without an endometriosis and no VTE history. Detailed information was captured using self-administered questionnaires at baseline and every 6 to 12 months thereafter. Self-reported VTEs were medically validated and reviewed by an independent adjudication committee. Incidence rates (IRs) were calculated per 10,000 woman-years. The association of endometriosis on VTE was determined in a time-to-event analysis, calculating crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) using stabilized inverse probability of treatment weighting (IPTW). A total of 22,072 women had an endometriosis diagnosis, and 91,056 women did not. Women with endometriosis contributed 78,751 woman-years during which 41 VTE events occurred (IR: 5.2/10,000, 95% CI: 3.7-7.1) compared to 127 VTEs during 310,501 woman-years in women without endometriosis (IR: 4.1/10,000, 95% CI: 3.4-4.9). The hazard ratio of VTE in women with endometriosis was 1.79 (95% CI: 1.24-2.57) using stabilized IPTW controlling for age, body mass index, smoking, education, age at menarche, and family history of VTE. Subgroup and sensitivity analyses showed similar results. These results highlight the importance of considering endometriosis as a potential factor contributing to VTE in women using OC; however, further research on the relationship between endometriosis and VTE is warranted.

Adjudication of Self-reported Symptomatic Stone Recurrence in the Prevention of Urinary Stones With Hydration Trial

ObjectiveTo assess accuracy of self-reported stone events in a large clinical trial by adjudication against the weight of documentation for spontaneous stone passage or surgical intervention. MethodsParticipants in the Prevention of Urinary Stones with Hydration (PUSH) trial were randomized to a multi-component behavioral intervention or control arm to increase and maintain high fluid intake. The primary endpoint was urinary stone events including symptomatic stone passage or procedural intervention. An independent adjudication committee blinded to randomization assignments reviewed all events. Confirmed clinical stone events required typical stone symptoms and documentation of stone passage (e.g., via photograph, clinical record) and/or surgical intervention. Events with typical symptoms and self-described stone passage but without objective documentation of passage were also considered as meeting the primary endpoint and classified separately as patient-reported passage. Non-events did not meet either criteria. ResultsAt time of this blinded analysis, a total of 1658 participants were randomized and had a median follow-up of 19 months. Self-reported stone events (n=217) were adjudicated by the committee as either confirmed clinical events (134; 61.8%), patient-reported passage (71; 32.7%), or non-events (12; 5.5%). Confirmed clinical events consisted of stone passage in 66/134 and procedural interventions in 68/134 (53 for symptoms and 15 without symptoms). ConclusionsRigorous adjudication revealed that self-reported stone events in the PUSH trial overwhelmingly represented clinically documented passage, surgical intervention, and patient-reported passage outside healthcare settings, with only 5.5% failing to satisfy adjudication criteria. Similar adjudication and classification processes warrant consideration for implementation in future stone trials. Clinical Trials RegistrationNCT03244189

789. EFFICACY AND SAFETY OF CRYOBALLOON-180 ABLATION FOR THE TREATMENT OF DYSPLASTIC BARRETT ESOPHAGUS: PRELIMINARY RESULTS FROM A PROSPECTIVE MULTICENTER STUDY

Abstract Background Cryoballoon-ablation is a relatively novel method for the eradication of dysplastic Barrett esophagus (BE). While the focal cryoballoon-ablation system has shown to be efficacious for BE of limited extent, the cryoballoon180-ablation system (CBAS180) is developed to treat longer BE segments by semi-circumferential ablation over 3cm, in a single step. A first-in-human study demonstrated the feasibility of CBAS180 treatment, yet the optimal dose needs to be determined. The current prospective, multicenter study, investigates CBAS180 at lower dosages for patients with dysplastic BE. Methods A total of 62 patients with ablation naïve BE (C≤3 and M≥1) will be enrolled in six Dutch Barrett expert centers. Treatment consists of a full circumferential ablation over 3 cm of length, using two semi-circumferential ablations at a dose of 1.2 mm/sec. Follow-up consisted of phone calls at days 1, 7 and 30, a symptom diary during 14 days, and an endoscopy after 3 months. Outcomes included (1) technical success rate; (2) BE regression percentage at follow-up scored by an independent adjudication committee; (3) incidence of adverse events; (4) post-procedural pain (scored on a scale of 0-10); and (5) post-procedural dysphagia (scored on a validated scale of 0-4). Follow-up treatment consisted of focal cryoballoon-ablation until complete eradication of visible BE was achieved, confirmed by biopsies from the neo-Z-line. Results So far, 25 patients (80% male; mean age 67) with a median BE length of C0M2 (p25-p75 C0-1M2-4) were included. Technical success rate was 92% (23/25; 95% CI 74-99%). In two patients, treatment was technically unsuccessful due to unstable positioning of the balloon (n=1) or a device malfunction (n=1). Median procedure time was 14 (p25-p75 11-16) 4) minutes and median ablation time was 5 (p25-p75 3-5) minutes. All 23 successfully treated patients completed follow-up endoscopy at 3 months. Median BE regression was 90% (p25-p75 75%-100%) evaluated by the independent adjudication committee. Overall, CBAS180 adverse event rate was 8% (2/23); one patient developed esophageal stricture (1/23; 4% [95% CI 1-16%]) resolved after a single endoscopic dilation. Another patient (1/23; 4% [95% CI 1-16%]) experienced post-procedural bleeding, with re-endoscopy without intervention. The CBAS180 procedure was well tolerated with low post-procedural pain (median 2 [p25-p75 1-4] at day 1 and 0 [p25-p75 0-1] at day 7) and dysphagia (56% and 70% of patients with score 0 at days 1 and 7, respectively) scores. So far, 22/23 (95%) patients were additionally treated with focal cryoballoon-ablation and 18/22 (82%) achieved a complete endoscopis and histologic eradication of BE after median 1 (p25-p75 1-3) treatment, the other 4 are still under treatment. After focal cryoballoon-ablation, 2/22 patients developed strictures, resolved after 1 and 2 endoscopic dilatations. Conclusion Based on these preliminary results, circumferential ablation with CBAS180 at 1.2 mm/sec, followed by focal cryoballoon-ablation, emerges as an effective and safe procedure for dysplastic BE eradication in the hands of expert endoscopists. Further avenues for exploration should encompass the assessment of multiple CBAS180 ablations stacked on top of each other in larger segments and the validation of outcomes in a larger patient cohort.

Enterprise Resource Planning Implementation: Challenges and Barriers

The goal of this study is to ascertain how Enterprise Resource Planning (ERP) adoption software is affected in small and medium-sized businesses in Jordan by the problems and barriers represented by (low knowledge of ERP, misperception, lack of resources, financial worries, and employee resistance). The following titles of employees in Jordanian small and medium-sized businesses' departments of information technology made up the study population: (Department Manager, Assistant Department Manager, Head of Department, and Software Officer). To accomplish the goals of the study, the investigator employed a basic random sample of the study population, wherein (160) questionnaires were distributed and (152) were retrieved. The descriptiveanalytic approach was employed in conjunction with various statistical techniques, the most notable of which was the "T" test for one sample (One SampleT–test), and the statistical package program was utilized for statistical analysis and testing of hypotheses. Use SPSS. The study's conclusions include the existence of a statistically significant relationship between Jordanian SMEs' software implementation and their lack of resources, financial concerns, and inadequate ERP understanding. On the other hand, misperception and employee resistance had no statistically significant effect on the implementation of software in Jordanian SMEs. In light of this, the study made several recommendations, the most significant of which is the establishment of an independent committee of senior management experts in information systems and information technology to monitor a variety of data regarding the readiness and effectiveness of the software. As well as involving the user in the ERP implementation from the beginning, because operations management may clearly and effectively benefit from the end-user's assistance in formulating operations that accurately and firmly fulfil daily work needs

Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial

BackgroundPeople with type 2 diabetes (T2D) and chronic kidney disease (CKD) are at high risk for heart failure (HF) and premature death from cardiovascular (CV) causes. The FLOW (Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease), which enrolled participants with T2D and CKD, demonstrated that semaglutide, a glucagon-like peptide-1 receptor agonist, reduced the incidence of the primary composite outcome (persistent ≥50% decline in estimated glomerular filtration rate, persistent estimated glomerular filtration rate <15 mL/min/1.73 m2, kidney replacement therapy, and kidney or CV death) by 24%. ObjectivesThis prespecified analysis examined the effects of semaglutide on HF outcomes in this high-risk population. MethodsParticipants were randomized (1:1) to once-weekly subcutaneous semaglutide 1 mg or placebo. The prespecified main outcome was a composite of HF events (new onset or worsening of HF leading to an unscheduled hospital admission or an urgent visit, with initiation of or intensified diuretic/vasoactive therapy) or CV death. HF data were collected by the investigator. CV death was adjudicated by an independent committee. ResultsA total of 3,533 randomized participants were followed for a median of 3.4 years. HF was present at baseline in 342 participants (19.4%) in the semaglutide group and 336 (19.0%) in the placebo group. In the overall trial population, semaglutide increased time to first HF events or CV death (HR: 0.73; 95% CI: 0.62-0.87; P = 0.0005), HF events alone (HR: 0.73; 95% CI: 0.58-0.92; P = 0.0068), and CV death alone (HR: 0.71; 95% CI: 0.56-0.89; P = 0.0036). The risk reduction for the composite HF outcome was similar in those with (HR: 0.73; 95% CI: 0.54-0.98; P = 0.0338) and without (HR: 0.72; 95% CI: 0.58-0.89; P = 0.0028) HF at baseline. The risk of HF outcomes (HF events or CV death) was generally higher in participants categorized as NYHA functional class III and those with the HF reduced ejection fraction subtype, regardless of treatment. ConclusionsSemaglutide substantially reduced the risk of time to first composite outcome of HF events or CV death, as well as HF events and CV death alone, in a high-risk population with T2D and CKD. These effects were consistent regardless of history of HF. (A Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease [FLOW]; NCT03819153)

PENGARUH FINANCIAL DISTRESS DAN CORPORATE GOVERNANCE TERHADAP KECEPATAN PUBLIKASI LAPORAN KEUANGAN TAHUNAN

The matter of submitting annual financial reports on time greatly affects the quality of the financial report itself. Financial reports are said to be of quality when information is presented on time and available when needed. The purpose of this study is to determine whether the condition of financial distress and the form of corporate governance of a company affect the speed of publication of annual financial reports. The study was conducted on companies engaged in the property and real estate sector and listed on the Indonesia Stock Exchange in 2021-2022. The purposive sampling technique was used to select samples with a total of 140 samples. The data in the study are secondary data. The data analysis technique is multiple linear analysis. The results of the study show that financial distress and corporate governance represented by managerial ownership and audit quality do not affect the speed of publication of annual financial reports. Meanwhile, corporate governance represented by independent commissioners, institutional ownership and audit committees have a negative effect on the speed of publication of annual financial reports