Benefit In Clinical Outcome Research Articles

Phosphatidylserine: A Novel Target for Ischemic Stroke Treatment.

Over the past 40 years, research has heavily emphasized stroke treatments that directly target ischemic cascades after stroke onset. Much attention has focused on studying neuroprotective drugs targeting one aspect of the ischemic cascade. However, the single-target therapeutic approach resulted in minimal clinical benefit and poor outcomes in patients. Considering the ischemic cascade is a multifaceted and complex pathophysiological process with many interrelated pathways, the spotlight is now shifting towards the development of neuroprotective drugs that affect multiple aspects of the ischemic cascade. Phosphatidylserine (PS), known as the "eat-me" signal, is a promising candidate. PS is involved in many pathophysiological changes in the central nervous system after stroke onset, including apoptosis, inflammation, coagulation, and neuronal regeneration. Moreover, PS might also exert various roles in different phases after stroke onset. In this review, we describe the synthesis, regulation, and function of PS under physiological conditions. Furthermore, we also summarize the different roles of PS after stroke onset. More importantly, we also discuss several treatment strategies that target PS. We aim to advocate a novel stroke care strategy by targeting PS through a translational perspective.

Leveraging programmed cell death signature to predict clinical outcome and immunotherapy benefits in postoperative bladder cancer

Bladder cancer is the fourth most common malignancy in men with poor prognosis. Programmed cell death (PCD) exerts crucial functions in many biological processes and immunotherapy responses of cancers. Cell death signature (CDS) is novel gene signature comprehensively considering the characteristics of 15 patterns of programmed cell death, which could affect the prognosis and immunotherapy benefits of cancer patients. Integrative machine learning procedure including 10 algorithms was conducted to construct a prognostic CDS using TCGA, GSE13507, GSE31684, GSE32984 and GSE48276 datasets. Immunophenoscore, intratumor heterogeneity (ITH), tumor immune dysfunction and exclusion (TIDE) score and five immunotherapy cohorts were used to evaluate the predictive value of CDS in immunotherapy response. The prognostic CDS constructed by StepCox[backward] + Ridge algorithms was regarded as the optimal prognostic model. The CDS had a stable and powerful performance in predicting overall survival of bladder cancer patients with the AUCs at 3-year, 5-year, and 7-year ROC of 0.740, 0.763 and 0.820 in TCGA cohort. Moreover, CDS score acted as an independent risk factor for overall survival rate of bladder cancer patients. Low CDS score had a higher abundance of immuno-activated cells, higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score, lower immune escape score, lower ITH score, lower cancer-related hallmarks score in bladder cancer. The CDS score was higher in non-responders in pan-cancer patients receiving immunotherapy. Our study constructed a novel prognostic CDS, which could serve as an indicator for predicting the prognosis in postoperative bladder cancer cases and immunotherapy benefits in pan-cancer. Low CDS score indicated a better prognosis and immunotherapy benefits.

Enhancing brain cancer type prediction through machine learning algorithms and feature selection techniques

Abstract The manual identification of brain cancer types is often fraught with inaccuracies, leading to potential delays in diagnosis and treatment planning. This study presents a novel approach to predict brain cancer types using advanced machine learning (ML) algorithms integrated with sophisticated feature selection techniques. A multi-class classification framework was developed and evaluated, incorporating six ML models: Bernoulli Naive Bayes, K-nearest neighbors classifier, decision tree classifier, Gaussian process classifier (GPC), passive aggressive classifier, and perceptron. To enhance model performance, feature selection methods including the Gini index, mutual information, and principal component analysis (PCA) were employed. A comprehensive case study was conducted to assess the predictive accuracy of these models. The GPC, when trained and validated on features derived via PCA, outperformed other models in terms of predictive accuracy and generalization. Specifically, the dimensions identified by PCA (d1, d2, d3, and d4) were most effective in distinguishing between different brain cancer types. This methodology resulted in a significant improvement across various performance metrics. Compared to the baseline GPC model using all original features, the PCA-enhanced GPC achieved remarkable increases in Accuracy, Precision, Recall, and F1 Score by 294.31%, 22.14%, 294.31%, and 878.18%, respectively. These findings underscore the potential of combining ML algorithms with targeted feature selection techniques to advance the accuracy of brain cancer type prediction, offering substantial benefits for clinical decision-making and patient outcomes.

The effect of the antibiotic stewardship program (ASP) on community-acquired pneumonia (CAP): a before-after study.

Background: Community-acquired pneumonia (CAP) is one of the leading causes of death worldwide. Antibiotic stewardship program (ASP) has been implemented to improve rational and responsible antibiotic use by encouraging guideline adherence. Objective: This retrospective observational before-after study aimed to evaluate whether the ASP may improve guideline adherence, antibiotic exposure, and clinical outcomes in patients hospitalized due to CAP in Hungary. Methods: The study was conducted at a pulmonology department of a tertiary care medical center in Hungary. The ASP implementation consisted of written and published guidelines available to all professionals, continuous supervision, and counseling services on antibiotic therapies at an individual level, with the aim of ensuring compliance with CAP guidelines. Overall guideline adherence (agent selection, route of administration, and dose), clinical outcomes (length of stay and 30-day mortality), antibiotic exposure, and direct costs were compared between the two periods. Fisher's exact test and t-test were applied to compare categorical and continuous variables, respectively. P-values below 0.05 were defined as significant. Results: Significant improvement in overall CAP guideline adherence (30.2%), sequential therapy (10.5%), and a significant reduction in the total duration of antibiotic therapy (13.5%) were observed. Guideline non-adherent combination therapies with metronidazole decreased significantly by 28.1%. Antibiotic exposure decreased by 7.2%, leading to a significant decrease in direct costs (23.6%). Moreover, the ASP had benefits for clinical outcomes, and length of stay decreased by 13.5%. Conclusion: The ASP may play an important role in optimizing empirical antibiotic therapy in CAP having a sustained long-term effect.

Machine learning developed an intratumor heterogeneity signature for predicting clinical outcome and immunotherapy benefit in bladder cancer.

Bladder cancer is a common malignancy with high invasion and poor clinical outcome. Intratumor heterogeneity (ITH) is linked to cancer progression and metastasis and high ITH can accelerate tumor evolution. Our objective is to develop an ITH-related signature (IRS) for predicting clinical outcome and immunotherapy benefit in bladder cancer. Integrative procedure containing ten machine learning methods was applied to develop an IRS with The Cancer Genome Atlas (TCGA), gene series expression (GSE)13507, GSE31684, GSE32984 and GSE48276 datasets. To evaluate the performance of IRS in predicting the immunotherapy benefit, we also used several predicting scores and three immunotherapy datasets, including GSE91061, GSE78220 and IMvigor210. The predicting model constructed with Enet (alpha =0.2) algorithm had a highest average C-index of 0.69, which was suggested as the optimal IRS. As an independent risk factor for bladder cancer, IRS had a powerful performance in predicting the overall survival (OS) rate of patients, with an area under curve of 1-, 3- and 5-year receiver operating characteristic (ROC) curve being 0.744, 0.791 and 0.816 in TCGA dataset. Bladder cancer patients with low IRS score presented with a higher level of immune-activated cells, cytolytic function and T cell co-stimulation. We also found a lower tumor immune dysfunction and exclusion (TIDE) score, lower immune escape score, higher programmed cell death protein 1 (PD-1) & cytotoxic T-lymphocyte associated protein 4 immunophenoscore, higher tumor mutation burden (TMB) score, higher response rate and better prognosis in bladder cancer with low IRS score. Bladder cancer cases with high IRS score had a higher half maximal inhibitory concentration value of common chemotherapy and targeted therapy regimens. The current study developed an optimal IRS for bladder cancer patients, which acted as an indicator for predicting prognosis, stratifying risk and guiding treatment for bladder cancer patients. Further analysis should be focused on the exploration the differentially expressed genes (DEGs) and related underlying mechanism mediating the development of bladder cancer in different IRS score group.

Innovation in pathogenesis and management of aortic aneurysm.

Aortic aneurysm (AA) refers to the persistent dilatation of the aorta, exceeding three centimeters. Investigating the pathophysiology of this condition is important for its prevention and management, given its responsibility for more than 25000 deaths in the United States. AAs are classified based on their location or morphology. various pathophysiologic pathways including inflammation, the immune system and atherosclerosis have been implicated in its development. Inflammatory markers such as transforming growth factor β, interleukin-1β, tumor necrosis factor-α, matrix metalloproteinase-2 and many more may contribute to this phenomenon. Several genetic disorders such as Marfan syndrome, Ehler-Danlos syndrome and Loeys-Dietz syndrome have also been associated with this disease. Recent years has seen the investigation of novel management of AA, exploring the implication of different immune suppressors, the role of radiation in shrinkage and prevention, as well as minimally invasive and newly hypothesized surgical methods. In this narrative review, we aim to present the new contributing factors involved in pathophysiology of AA. We also highlighted the novel management methods that have demonstrated promising benefits in clinical outcomes of the AA.

Implementation, Clinical Benefit and Safety of a D-Dimer-Focused Pulmonary Embolism Testing Pathway in the Emergency Department

Computed tomography pulmonary angiogram (CTPA) is overused during pulmonary embolism (PE) testing in the emergency department (ED), whereas prediction rules and D-dimer are underused. We report the adherence, clinical benefit, and safety of a D-dimer-only strategy to guide need for PE imaging in the ED. This was a prospective multicenter implementation study in 2 EDs with historical and external controls. Patients with suspected PE underwent D-dimer testing and imaging (CTPA or ventilation-perfusion scan) when D-dimer levels were 500 ng/mL or more. PE was ruled out if D-dimer was less than 500 ng/mL or with negative imaging. The primary implementation outcome was the proportion of patients tested for PE in adherence with the pathway. The primary clinical benefit outcome was the proportion of patients tested for PE who received pulmonary imaging. The primary safety outcome was diagnosis of PE in the 30 days following negative PE testing postimplementation. Between January 2018 and June 2021, 16,155 patients were tested for PE, including 33.4% postimplementation, 30.7% preimplementation, and 35.9% in an external control site. Adherence with the D-dimer-only pathway was 97.6% (adjusted odds ratio (aOR) post- versus preimplementation 5.26 (95% confidence interval 1.70 to 16.26). There was no effect on the proportion undergoing PE imaging. Imaging yield increased aOR 4.89 (1.17 to 20.53). Two cases of PE (0.04%; 0.01% to 0.16%) were diagnosed within 30 days. In this Canadian ED study, the uptake of a D-dimer-only PE testing strategy was high. Implementation was associated with higher imaging yield and a D-dimer level of less than 500 ng/mL safely excluded PE.

Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval

The US Food and Drug Administration's (FDA) accelerated approval pathway allows approval of investigational drugs treating unmet medical needs based on changes to surrogate measures considered "reasonably likely" to predict clinical benefit. Postapproval clinical trials are then required to confirm whether these drugs offer clinical benefit. To determine whether cancer drugs granted accelerated approval ultimately demonstrate clinical benefit and to evaluate the basis of conversion to regular approval. In this cohort study, publicly available FDA data were used to identify cancer drugs granted accelerated approval from 2013 to 2023. Demonstrated improvement in quality of life or overall survival in accelerated approvals with more than 5 years of follow-up, as well as confirmatory trial end points and time to conversion for drug-indication pairs converted to regular approval. A total of 129 cancer drug-indication pairs were granted accelerated approval from 2013 to 2023. Among 46 indications with more than 5 years of follow-up (approved 2013-2017), approximately two-thirds (29, 63%) were converted to regular approval, 10 (22%) were withdrawn, and 7 (15%) remained ongoing after a median of 6.3 years. Fewer than half (20/46, 43%) demonstrated a clinical benefit in confirmatory trials. Time to withdrawal decreased from 9.9 years to 3.6 years, and time to regular approval increased from 1.6 years to 3.6 years. Among 48 drug-indication pairs converted to regular approval, 19 (40%) were converted based on overall survival, 21 (44%) on progression-free survival, 5 (10%) on response rate plus duration of response, 2 (4%) on response rate, and 1 (2%) despite a negative confirmatory trial. Comparing accelerated and regular approval indications, 18 of 48 (38%) were unchanged, while 30 of 48 (63%) had different indications (eg, earlier line of therapy). Most cancer drugs granted accelerated approval did not demonstrate benefit in overall survival or quality of life within 5 years of accelerated approval. Patients should be clearly informed about the cancer drugs that use the accelerated approval pathway and do not end up showing benefits in patient-centered clinical outcomes.

Atelocollagen Injection During Arthroscopic Rotator Cuff Repair for Small- to Medium-Sized Subacute or Chronic Rotator Cuff Tears Enhances Radiographic Tendon Integrity: A Propensity Score–Matched Comparative Study

PurposeTo evaluate the clinical and structural outcomes of using injectable atelocollagen during arthroscopic rotator cuff repair (ARCR) for small to medium-sized rotator cuff tears. MethodsThis retrospective study reviewed patients with small to medium size full-thickness tears who underwent ARCR from 2016 to 2022 with minimum 1 year follow-up. Propensity score (PS) matching was used to reduce bias. Tendon integrity was evaluated using magnetic resonance imaging (MRI) at postoperative 6 months. Clinical and structural outcomes were compared between the two groups. ResultsAfter PS matching, this study included 181 pairs of patients comparing ARCR with atelocollagen injection and without atelocollagen injection. Range of Motion, muscle strength, and functional outcomes were significantly improved in both the atelocollagen group and the control group. Forward elevation and external rotation were significantly worse in the atelocollagen group compared to the control group at 2, 6, 12 months postoperatively and at final follow-up. 125 patients (69.1%) in the atelocollagen group and 130 patients (71.8%) in the control group exceeded the MCID in ASES score without significant difference between the two groups (P = .509). The mean value of Sugaya grade on postoperative MRI evaluation was 2.03 ± 0.81 for the atelocollagen group and 2.24 ± 0.97 for the control group with a significant difference between the two groups (P = .027). Tendon healing failure was observed in 12 patients (6.6%) in the atelocollagen group and 19 patients (10.5%) in the control group with no statistical difference between the two groups (P = .189). ConclusionAtelocollagen injection during arthroscopic rotator cuff repair for small- to medium-sized subacute or chronic rotator cuff tears did not show benefit in clinical outcomes. However, postoperative MRI showed significantly lower Sugaya grade compared to the control group, with no significant difference in retear rate. Level of evidenceIII, Retrospective case-control study

Inhaled treprostinil in patients with pulmonary hypertension associated with interstitial lung disease with less severe haemodynamics: a post hoc analysis of the INCREASE study

BackgroundInhaled treprostinil (iTre) is the only treatment approved for pulmonary hypertension due to interstitial lung disease (PH-ILD) to improve exercise capacity. This post hoc analysis evaluated clinical worsening and PH-ILD...

Telemedical stroke care significantly improves patient outcome in rural areas: Long-term analysis of the German NEVAS network.

Comprehensive stroke centers (CSC) offer state-of-the-art stroke care in metropolitan centers. However, in rural areas, sufficient stroke expertise is much scarcer. Recently, telemedical stroke networks have offered instant consultation by stroke experts, enabling immediate administration of intravenous thrombolysis (IVT) on-site and decision on thrombectomy. While these immediate decisions are made during the consult, the impact of the network structures on stroke care in spoke hospitals is still not well described. This study was performed to determine if on-site performance in rural hospitals and patient outcome improve over time through participation and regular medical staff training within a telemedical stroke network. In this retrospective study, we analyzed data from stroke patients treated in four regional hospitals within the telemedical Neurovascular Network of Southwest Bavaria (NEVAS) between 2014 and 2019. We only included those patients that were treated in the regional hospitals until discharge at home or to neurorehabilitation. Functional outcome (modified Rankin scale) at discharge, mortality rate and periprocedural intracranial hemorrhage served as primary outcome parameters. Door-to-imaging and door-to-needle times were secondary outcome parameters. In 2014-2019, 5,379 patients were treated for acute stroke with 477 receiving IVT. Most baseline characteristics were comparable over time. For all stroke patients, door-to-imaging times increased over the years, but significantly improved for potential IVT candidates and those finally treated with IVT. The percentage of patients with door-to-needle time <30 min increased from 10% to 25%. Clinical outcome at discharge improved for all stroke patients treated in the regional hospitals. Particularly for patients treated with IVT, good clinical outcome (modified Rankin scale 0-2) at discharge increased from 2014 to 2019 by 19% and mortality rates dropped from 13% to 5%. 24-h/7-day telemedical support and regular on-site medical staff training within a structured telemedicine stroke network such as NEVAS significantly improve on-site stroke care in rural areas, leading to a considerable benefit in clinical outcome. The data that support the findings of this study are available upon reasonable request and in compliance with the local and international ethical guidelines.

Effect of different starting doses of FSH on laboratory and clinical outcomes in patients with moderate AMH level.

IVF and ICSI-ET are widely used ART for addressing infertility which have been developed and improved over the last four decades. COS is a crucial step in IVF/ICSI-ET, whereby medications stimulate the ovaries to produce multiple eggs. The success of the procedure depends on the number of eggs retrieved, and individualized ovarian stimulation protocols based on factors like age and ovarian reserve can optimize the chances of obtaining mature oocytes. The optimal starting dose of FSH at moderate AMH levels remains a topic of debate., tThis study aims to compare different starting doses of FSH in clinical outcomes by analyzing data from a single center. This retrospective study collected clinical material from patients with moderate AMH levels at 1.2 ~ 4.5ng/mL who received IVF/ICSI-ET under a follicular phase long protocol from July 2018 to December 2021 at Guiyang Maternal and Child Health Care Hospital, China. The patients' clinical data were retrieved from the hospital's software database and divided into two groups based on FSH starting dose, as follows: lower starting dose group: FSH ≤ 150IU; and higher starting dose group: FSH > 150IU. Multiple laboratory and clinical outcomes were compared between the two groups. A total of 1784 patients with moderate serum AMH levels who received IVF/ICSI-ET under a follicular phase long protocol were enrolled based on eligibility criteria. In the population with moderate AMH levels, a lower starting dose of FSH might have more benefit than a higher starting dose in numbers of follicles with diameters ≥ 14mm and < 16mm, ≥ 16mm and < 18mm, and ≥ 18mm; numbers of retrieved oocytes, 2PNs, transferable embryos, high-quality embryos, and cleavage stage embryos transferred; and clinical pregnancy rate, intrauterine pregnancy rate, and parturition rate. Moreover, rFSH had a statistically significantly higher number of oocytes retrieved, number of 2PNs, and number of transferable embryos than that of patients who received uFSH. The starting dose of FSH in the moderate AMH population remains controversial and a higher starting dose may not lead to more benefit in laboratory and clinical outcomes.

Rivaroxaban vs Vitamin K Antagonist in Patients With Atrial Fibrillation and Advanced Chronic Kidney Disease

BackgroundTreatment with vitamin K antagonists (VKAs) has been linked to worsening of kidney function in patients with atrial fibrillation (AF). ObjectivesXARENO (Factor XA-inhibition in RENal patients with non-valvular atrial fibrillation Observational registry; NCT02663076) is a prospective observational study comparing adverse kidney outcomes in patients with AF and advanced chronic kidney disease receiving rivaroxaban or VKA. MethodsPatients with AF and an estimated glomerular filtration rate (eGFR) of 15 to 49 mL/min/1.73 m2 were included. Blinded adjudicated outcome analysis evaluated adverse kidney outcomes (a composite of eGFR decline to <15 mL/min/1.73 m2, need for chronic kidney replacement therapy, or development of acute kidney injury). A composite net clinical benefit outcome (stroke or systemic embolism, major bleeding, myocardial infarction, acute coronary syndrome, or cardiovascular death) was also analyzed. HRs with 95% CIs were calculated using propensity score overlap weighting Cox regression. ResultsThere were 1,455 patients (764 rivaroxaban; 691 VKA; mean age 78 years; 44% females). The mean eGFR was 37.1 ± 9.0 in those receiving rivaroxaban and 36.4 ± 10.1 mL/min/1.73 m2 in those receiving VKA. After a median follow-up of 2.1 years, rivaroxaban was associated with less adverse kidney outcomes (HR: 0.62; 95% CI: 0.43-0.88) and all-cause death (HR: 0.76, 95% CI: 0.59-0.98). No significant differences were observed in net clinical benefit. ConclusionsIn patients with AF and advanced chronic kidney disease, those receiving rivaroxaban had less adverse kidney events and lower all-cause mortality compared to those receiving VKA, supporting the use of rivaroxaban in this high-risk group of patients.

Expression of pro- and anti-inflammatory cytokines during anti-proprotein convertase subtilisin/kexin type 9 therapy in patients with statin-resistant familial hypercholesterolemia.

Some clinical dyslipidemia cases do not respond to statins, known as statin-resistant familial hypercholesterolemia (SR-FH), in which patients are under a high cardiovascular risk despite statin therapy. Therefore, novel therapeutic alternatives are required. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduce cholesterol levels and cardiovascular disease risk, particularly in patients with SR-FH, where PCSK9i may differentially affect pro- and anti-inflammatory mediators depending on the clinical setting. To evaluate the effect of PCSK9i treatment on pro- and anti-inflammatory cytokines in patients with SR-FH. Before-after comparison, quasi-experimental, single-center study in patients with SR-FH. Blood samples were processed to obtain complete blood counts of glycated hemoglobin and serum lipid levels. Flow cytometry was performed to characterize baseline circulating M1- and M2-macrophages and monocytes. Multiplexing of plasma samples was used to compare plasma fraktaline, interleukins (ILs), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha. The endpoints were lower serum lipid levels and pro-inflammatory mediator modification. Twenty patients with SR-FH, aged 58 years and most of them males, were included, with a mean body-mass index of 26.4 and showing ischemic heart disease and similar values of baseline M1- and M2-macrophages and monocytes. Six-month iPSCK-9 therapy considerably reduced LDLc, increased anti-inflammatory cytokine (IL-4), and modified pro-inflammatory cytokine (TNF-alpha and MCP-1) levels. No notable effects were observed for the other markers. PCSK9i therapy exerted subclinical anti-inflammatory and anti-atherogenic effects, indicating potential benefits for clinical outcomes.

Role of intravascular ultrasound and optical coherence tomography in intracoronary imaging for coronary artery disease: a systematic review.

Coronary angiography has long been the standard for coronary imaging, but it has limitations in assessing vessel wall anatomy and guiding percutaneous coronary intervention (PCI). Intracoronary imaging techniques like intravascular ultrasound (IVUS) and optical coherence tomography (OCT) can overcome these limitations. IVUS uses ultrasound and OCT uses near-infrared light to visualize coronary pathology in unique ways due to differences in temporal and spatial resolution. These techniques have evolved to offer clinical utility in plaque characterization and vessel assessment during PCI. Meta-analyses and adjusted observational studies suggest that both IVUS and OCT-guided PCI correlate with reduced cardiovascular risks compared to angiographic guidance alone. While IVUS demonstrates consistent clinical outcome benefits, OCT evidence is less robust. IVUS has progressed from early motion detection to high-resolution systems, with smaller compatible catheters. OCT utilizes near infrared light to achieve unparalleled resolutions, but requires temporary blood clearance for optimal imaging. Enhanced visualization and guidance make IVUS and OCT well-suited for higher risk PCI in patients with diabetes and chronic kidney disease by allowing detailed visualization of complex lesions and ensuring optimal stent deployment and positioning in PCI for patients with type 2 diabetes and chronic kidney disease, improving outcomes. IVUS and recent advancements in zero- and low-contrast OCT techniques can reduce nephrotoxic contrast exposure, thus helping to minimize PCI complications in these high-risk patient groups. IVUS and OCT provide valuable insights into coronary pathophysiology and guide interventions precisely compared to angiography alone. Both have comparable clinical outcomes, emphasizing the need for tailored imaging choices based on clinical scenarios. Continued refinement and integration of intravascular imaging will likely play a pivotal role in optimizing coronary interventions and outcomes. This systematic review aims to delve into the nuances of IVUS and OCT, highlighting their strengths and limitations as PCI adjuncts.

Communication aspects of doctor-patient interrelationship

The medical act is based, including, on the doctor-patient relationship, which can have positive or negative influences on patient satisfaction, compliance, clinical and, finally, economic results. This article presents a synthesis of publications from the relevant scientific literature, addresses the importance of the doctor-patient relationship and communication aspects. The analyzed sources confirm that the interaction between doctor and patient is the central and critical element of medical services, and communication skills (empathy, verbal and nonverbal aspects, motivational interviewing, decision-making collaboration, etc.) can be learned and developed, which will bring benefits for clinical outcomes and will increase the quality of life and patient satisfaction with the medical system.

Barriers and Facilitators Associated With Remote Monitoring Adherence Among Veterans With Pacemakers and Implantable Cardioverter-Defibrillators: Qualitative Cross-Sectional Study.

The Heart Rhythm Society strongly recommends remote monitoring (RM) of cardiovascular implantable electronic devices (CIEDs) because of the clinical outcome benefits to patients. However, many patients do not adhere to RM and, thus, do not achieve these benefits. There has been limited study of patient-level barriers and facilitators to RM adherence; understanding patient perspectives is essential to developing solutions to improve adherence. We sought to identify barriers and facilitators associated with adherence to RM among veterans with CIEDs followed by the Veterans Health Administration. We interviewed 40 veterans with CIEDs regarding their experiences with RM. Veterans were stratified into 3 groups based on their adherence to scheduled RM transmissions over the past 2 years: 6 fully adherent (≥95%), 25 partially adherent (≥65% but <95%), and 9 nonadherent (<65%). As the focus was to understand challenges with RM adherence, partially adherent and nonadherent veterans were preferentially weighted for selection. Veterans were mailed a letter stating they would be called to understand their experiences and perspectives of RM and possible barriers, and then contacted beginning 1 week after the letter was mailed. Interviews were structured (some questions allowing for open-ended responses to dive deeper into themes) and focused on 4 predetermined domains: knowledge of RM, satisfaction with RM, reasons for nonadherence, and preferences for health care engagement. Of the 44 veterans contacted, 40 (91%) agreed to participate. The mean veteran age was 75.3 (SD 7.6) years, and 98% (39/40) were men. Veterans had been implanted with their current CIED for an average of 4.4 (SD 2.8) years. A total of 58% (23/40) of veterans recalled a discussion of home monitoring, and 45% (18/40) reported a good understanding of RM; however, when asked to describe RM, their understanding was sometimes incomplete or not correct. Among the 31 fully or partially adherent veterans, nearly all were satisfied with RM. Approximately one-third recalled ever being told the results of a remote transmission. Among partially or nonadherent veterans, only one-fourth reported being contacted by a Department of Veterans Affairs health care professional regarding not having sent a remote transmission; among those who had troubleshooted to ensure they could send remote transmissions, they often relied on the CIED manufacturer for help (this experience was nearly always positive). Most nonadherent veterans felt more comfortable engaging in RM if they received more information or education. Most veterans were interested in being notified of a successful remote transmission and learning the results of their remote transmissions. Veterans with CIEDs often had limited knowledge about RM and did not recall being contacted about nonadherence. When they were contacted and troubleshooted, the experience was positive. These findings provide opportunities to optimize strategies for educating and engaging patients in RM.

Administration of corticosteroid therapy for HELLP syndrome in pregnant women: evidences from seven randomized controlled trials

ABSTRACT Background HELLP syndrome, featuring hemolysis, elevated liver enzymes, and thrombocytopenia, is life-threatening disease of pregnancy that triggers comorbidities in both pregnant women and the fetus/newborn. This study provides an updated systematic review and meta-analysis of relevant studies to assess the therapeutic efficacy of corticosteroids in maternal and neonatal outcomes. Methods Randomized control trials (RCTs) regarding the use of corticosteroids in the HELLP population from three electronic databases, including Ovid MEDLINE, Ovid EMBASE, andCochrane Central Register of Controlled Trials, were searched from database inception to 23 March 202323 March 2023. Results A total of 485 patients treated with corticosteroids from 7 RCTs were included. Compared to placebo, corticosteroids therapy failed to significantly improve the maternal outcomes regard to maternal morbidity (RR = 1.36, 95%CI [0.45, 4.10]), eclampsia (RR = 1.16, 95%CI [0.76, 1.77]), acute renal failure (RR = 0.71, 95%CI [0.41, 1.22]), pulmonary edema (RR = 0.34, 95%CI [0.10, 1.15]) and oliguria (RR = 1.08, 95%CI [0.75, 1.54]). In addition, pooled data showed that it wasn’t significant differences between corticosteroids therapy and placebo regarding neonatal outcomes. Conclusions This study compared the efficacy of corticosteroids in patients with HELLP syndrome, revealing that corticosteroids did not provide any significant benefit in clinical outcomes for pregnant women and newborns with HELLP. The conclusions of this study must be verified by a larger sample of high-quality RCTs.

Incremental versus conventional haemodialysis in end-stage kidney disease: a systematic review and meta-analysis.

Appropriate dialysis prescription in the transitional setting from chronic kidney disease to end-stage kidney disease is still challenging. Conventional thrice-weekly haemodialysis (HD) might be associated with rapid loss of residual kidney function (RKF) and high mortality. The benefits and risks of incremental HD compared with conventional HD were explored in this systematic review and meta-analysis. We searched MEDLINE, Scopus and Cochrane Central Register of Controlled Trials up to April 2023 for studies that compared the impacts of incremental (once- or twice-weekly HD) and conventional thrice-weekly HD on cardiovascular events, RKF, vascular access complications, quality of life, hospitalization and mortality. A total of 36 articles (138939 participants) were included in this meta-analysis. The mortality rate and cardiovascular events were similar between incremental and conventional HD {odds ratio [OR] 0.87 [95% confidence interval (CI)] 0.72-1.04 and OR 0.67 [95% CI 0.43-1.05], respectively}. However, hospitalization and loss of RKF were significantly lower in patients treated with incremental HD [OR 0.44 (95% CI 0.27-0.72) and OR 0.31 (95% CI 0.25-0.39), respectively]. In a sensitivity analysis that included studies restricted to those with RKF or urine output criteria, incremental HD had significantly lower cardiovascular events [OR 0.22 (95% CI 0.08-0.63)] and mortality [OR 0.54 (95% CI 0.37-0.79)]. Vascular access complications, hyperkalaemia and volume overload were not statistically different between groups. Incremental HD has been shown to be safe and may provide superior benefits in clinical outcomes, particularly in appropriately selected patients. Large-scale randomized controlled trials are required to confirm these potential advantages.

Aligning US Agency Policies for Cardiovascular Devices Through the Breakthrough Devices Program

The US Food and Drug Administration (FDA) and Centers for Medicare & Medicaid Services (CMS) have different statutory authorities; FDA evaluates safety and effectiveness for market authorization of medical devices while CMS determines whether coverage is "reasonable and necessary" for its beneficiaries. CMS has recently enacted policies automatically providing supplemental reimbursement for new, costly devices authorized after designation in FDA's Breakthrough Devices Program (BDP) and in June 2023 issued notice for a new Transitional Coverage for Emerging Technologies pathway, accelerating coverage for Breakthrough devices. Aiming to incentivize innovation, FDA awards Breakthrough designations early in device development to expedite market authorization and can accept greater uncertainty in benefit and risk, contingent on postmarket evidence generation. Since 2020, Breakthrough designation has effectively automatically qualified devices to receive supplemental Medicare reimbursement after CMS waived a long-standing requirement that devices demonstrate "substantial clinical improvement" for beneficiaries. Using publicly available information, 3 examples of cardiovascular devices illustrate that the BDP may allow for FDA authorization based on less rigorous evidence, such as single-arm trials focused on surrogate end points with short-term follow-up whose participants are often not representative of Medicare beneficiaries. In 1 case, Breakthrough designation allowed a 30% decrease in enrollment of a trial used to support approval. Initial positive findings for some devices have remained unverified, and in 1 case even partially nullified, by postmarket studies. Manufacturers have also used Breakthrough designations to set the price of devices to facilitate additional pass-through payments, leading to higher short-term and long-term costs to CMS and health care systems. The BDP may qualify new, costly devices for higher and automatic Medicare reimbursement despite evidence not being representative of CMS beneficiaries and persistent uncertainty of benefit and risk. To ensure the best evidence is generated to inform clinical care, FDA could apply more selectivity to BDP eligibility, specify objective criteria for revoking Breakthrough designation when appropriate, and ensure timely postmarket evidence generation, whereas CMS could independently review clinical evidence, advise manufacturers about standards for coverage review, and make supplemental payments and long-term device reimbursement contingent on clinical outcome benefit and postmarket evidence generation.