The latest medical research on Healthcare

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about healthcare gathered by our medical AI research bot.

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Highly Accurate Blood Test for Alzheimer's Disease Comparable or Superior to Clinical CSF Tests.

Nature Medicine

With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes cr...

A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis.

N Engl J

Effective treatments for patients with primary biliary cholangitis are limited. Seladelpar, a peroxisome proliferator-activated receptor delta agonist, has potential benefits.

In this phase 3, 12-month, double-blind, placebo-controlled trial, we randomly assigned (in a 2:1 ratio) patients who had had an inadequate response to or who had a history of unacceptable side effects with ursodeoxycholic acid to receive oral seladelpar at a dose of 10 mg daily or placebo. The primary end point was a biochemical response, which was defined as an alkaline phosphatase level less than 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level at month 12. Key secondary end points were normalization of the alkaline phosphatase level at month 12 and a change in the score on the pruritus numerical rating scale (range, 0 [no itch] to 10 [worst itch imaginable]) from baseline to month 6 among patients with a baseline score of at least 4 (indicating moderate-to-severe pruritus).

Of the 193 patients who underwent randomization and treatment, 93.8% received ursodeoxycholic acid as standard-of-care background therapy. A greater percentage of the patients in the seladelpar group than in the placebo group had a biochemical response (61.7% vs. 20.0%; difference, 41.7 percentage points; 95% confidence interval [CI], 27.7 to 53.4, P<0.001). Normalization of the alkaline phosphatase level also occurred in a greater percentage of patients who received seladelpar than of those who received placebo (25.0% vs. 0%; difference, 25.0 percentage points; 95% CI, 18.3 to 33.2, P<0.001). Seladelpar resulted in a greater reduction in the score on the pruritus numerical rating scale than placebo (least-squares mean change from baseline, -3.2 vs. -1.7; least-squares mean difference, -1.5; 95% CI, -2.5 to -0.5, P = 0.005). Adverse events were reported in 86.7% of the patients in the seladelpar group and in 84.6% in the placebo group, and serious adverse events in 7.0% and 6.2%, respectively.

In this trial involving patients with primary biliary cholangitis, the percentage of patients who had a biochemical response and alkaline phosphatase normalization was significantly greater with seladelpar than with placebo. Seladelpar also significantly reduced pruritus among patients who had moderate-to-severe pruritus at baseline. The incidence and severity of adverse events were similar in the two groups. (Funded by CymaBay Therapeutics; RESPONSE ClinicalTrials.gov number, NCT04620733; EudraCT number, 2020-004348-27.).

CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up.

N Engl J

Treatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission.

We evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide. Efficacy up to 2 years after CAR T-cell infusion was assessed by means of Definition of Remission in SLE (DORIS) remission criteria, American College of Rheumatology-European League against Rheumatism (ACR-EULAR) major clinical response, and the score on the European Scleroderma Trials and Research Group (EUSTAR) activity index (with higher scores indicating greater disease activity), among others. Safety variables, including cytokine release syndrome and infections, were recorded.

The median follow-up was 15 months (range, 4 to 29). The mean (±SD) duration of B-cell aplasia was 112±47 days. All the patients with SLE had DORIS remission, all the patients with idiopathic inflammatory myositis had an ACR-EULAR major clinical response, and all the patients with systemic sclerosis had a decrease in the score on the EUSTAR activity index. Immunosuppressive therapy was completely stopped in all the patients. Grade 1 cytokine release syndrome occurred in 10 patients. One patient each had grade 2 cytokine release syndrome, grade 1 immune effector cell-associated neurotoxicity syndrome, and pneumonia that resulted in hospitalization.

In this case series, CD19 CAR T-cell transfer appeared to be feasible, safe, and efficacious in three different autoimmune diseases, providing rationale for further controlled clinical trials. (Funded by Deutsche Forschungsgemeinschaft and others.).

Biomarker Changes during 20 Years Preceding Alzheimer's Disease.

N Engl J

Biomarker changes that occur in the period between normal cognition and the diagnosis of sporadic Alzheimer's disease have not been extensively investigated in longitudinal studies.

We conducted a multicenter, nested case-control study of Alzheimer's disease biomarkers in cognitively normal participants who were enrolled in the China Cognition and Aging Study from January 2000 through December 2020. A subgroup of these participants underwent testing of cerebrospinal fluid (CSF), cognitive assessments, and brain imaging at 2-year-to-3-year intervals. A total of 648 participants in whom Alzheimer's disease developed were matched with 648 participants who had normal cognition, and the temporal trajectories of CSF biochemical marker concentrations, cognitive testing, and imaging were analyzed in the two groups.

The median follow-up was 19.9 years (interquartile range, 19.5 to 20.2). CSF and imaging biomarkers in the Alzheimer's disease group diverged from those in the cognitively normal group at the following estimated number of years before diagnosis: amyloid-beta (Aβ)42, 18 years; the ratio of Aβ42 to Aβ40, 14 years; phosphorylated tau 181, 11 years; total tau, 10 years; neurofilament light chain, 9 years; hippocampal volume, 8 years; and cognitive decline, 6 years. As cognitive impairment progressed, the changes in CSF biomarker levels in the Alzheimer's disease group initially accelerated and then slowed.

In this study involving Chinese participants during the 20 years preceding clinical diagnosis of sporadic Alzheimer's disease, we observed the time courses of CSF biomarkers, the times before diagnosis at which they diverged from the biomarkers from a matched group of participants who remained cognitively normal, and the temporal order in which the biomarkers became abnormal. (Funded by the Key Project of the National Natural Science Foundation of China and others; ClinicalTrials.gov number, NCT03653156.).

Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera.

N Engl J

Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide, an injectable peptide mimetic of the master iron regulatory hormone hepcidin, restricts the availability of iron for erythropoiesis. The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown.

In part 1 of the international, phase 2 REVIVE trial, we enrolled patients in a 28-week dose-finding assessment of rusfertide. Part 2 was a double-blind, randomized withdrawal period in which we assigned patients, in a 1:1 ratio, to receive rusfertide or placebo for 12 weeks. The primary efficacy end point was a response, defined by hematocrit control, absence of phlebotomy, and completion of the trial regimen during part 2. Patient-reported outcomes were assessed by means of the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) patient diary (scores range from 0 to 10, with higher scores indicating greater severity of symptoms).

Seventy patients were enrolled in part 1 of the trial, and 59 were assigned to receive rusfertide (30 patients) or placebo (29 patients) in part 2. The estimated mean (±SD) number of phlebotomies per year was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). The mean maximum hematocrit was 44.5±2.2% during part 1 as compared with 50.0±5.8% during the 28 weeks before the first dose of rusfertide. During part 2, a response was observed in 60% of the patients who received rusfertide as compared with 17% of those who received placebo (P = 0.002). Between baseline and the end of part 1, rusfertide treatment was associated with a decrease in individual symptom scores on the MPN-SAF in patients with moderate or severe symptoms at baseline. During parts 1 and 2, grade 3 adverse events occurred in 13% of the patients, and none of the patients had a grade 4 or 5 event. Injection-site reactions of grade 1 or 2 in severity were common.

In patients with polycythemia vera, rusfertide treatment was associated with a mean hematocrit of less than 45% during the 28-week dose-finding period, and the percentage of patients with a response during the 12-week randomized withdrawal period was greater with rusfertide than with placebo. (Funded by Protagonist Therapeutics; REVIVE ClinicalTrials.gov number, NCT04057040.).

The effect of ultrasound-assisted thrombolysis studied in blood-on-a-chip.

Journal of Artificial Intelligence Research

Thromboembolism, which leads to pulmonary embolism and ischemic stroke, remains one of the main causes of death. Ultrasound-assisted thrombolysis (UAT) is an effective thrombolytic method. However, further studies are required to elucidate the mechanism of ultrasound on arterial and venous thrombi.

We employed the blood-on-a-chip technology to simulate thrombus formation in coronary stenosis and deep vein valves. Subsequently, UAT was conducted on the chip to assess the impact of ultrasound on thrombolysis under varying flow conditions. Real-time fluorescence was used to assess thrombolysis and drug penetration. Finally, scanning electron microscopy and immunofluorescence were used to determine the effect of ultrasound on fibrinolysis.

The study revealed that UAT enhanced the thrombolytic rate by 40% in the coronary stenosis chip and by 10% in the deep venous valves chip. This enhancement is attributed to the disruption of crosslinked fibrin fibers by ultrasound, leading to increased urokinase diffusion within the thrombus and accumulation of plasminogen on the fibrinogen α chain. Moreover, the acceleration of the dissolution rate of thrombi in the venous valve chip by ultrasound was not as significant as that in the coronary stenosis chip.

These findings highlight the differential impact of ultrasound on thrombolysis under various flow conditions and emphasize the valuable role of the blood-on-a-chip technology in exploring thrombolysis mechanisms.

Intracorporeal LVAD implantation in pediatric patients: A single-center 10 years' experience.

Journal of Artificial Intelligence Research

Mechanical cardiac support is currently an effective strategy to reduce morbidity and mortality in pediatric patients. However, solid evidence regarding the feasibility of intracorporeal devices in children still needs to be provided. We report our 10-year experience with intracorporeal left ventricular assist devices (LVAD) in children.

We included all patients undergoing intracorporeal, continuous-flow LVAD implantation between 2012 and 2022. Baseline and postoperative data were collected from the institutional database.

Seven HeartWare and 4 HeartMate3 were implanted in 11 patients (median age 13.9 years, median body surface area - BSA - 1.42 m2 , IQR 1.06-1.68). The most frequent indication to LVAD implant was dilated cardiomyopathy (72.7%). All candidates underwent a thorough preoperative advanced imaging. Three-dimensional reconstructions and implant fit simulation were performed when BSA was <1.2 m2 , weight <30 kg, or internal transverse thoracic diameter <20 cm. There was no operative death. The most common postoperative complication was surgical re-exploration due to bleeding (27.3%). One patient died of severe neurological complications after about 3 months of hospitalization. No late deaths or unplanned re-hospitalizations occurred in the remaining 10, 6 of whom were discharged home. There were no major complications at the follow-up. All survivors underwent successful heart transplantation.

Intracorporeal LVAD implantation proved to be a potentially feasible and safe option in young teenagers and children whose BSA was >1.0 m2 . In borderline cases, the 3D reconstruction with implant fit simulation can effectively help to identify those patients who can safely undergo intrathoracic LVAD implantation.

Clinical surveillance systems obscure the true cholera infection burden in an endemic region.

Nature Medicine

Our understanding of cholera transmission and burden largely relies on clinic-based surveillance, which can obscure trends, bias burden estimates a...

Selection, optimization and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse US populations.

Nature Medicine

Polygenic risk scores (PRSs) have improved in predictive performance, but several challenges remain to be addressed before PRSs can be implemented ...

Consumer perspectives of allied health involvement in a public hospital setting: cross-sectional survey and electronic health record review.

Aust Health Rev

ObjectiveConsumer-centred care is fundamental to high-quality health care, with allied health professionals playing a pivotal role in hospital sett...

The impact of self-assessment and surveyor assessment on site visit performance under the National General Practice Accreditation scheme.

Aust Health Rev

ObjectiveThere is a need to undertake more proactive and in-depth analyses of general practice accreditation processes. Two areas that have been hi...

Who smokes in Australia? Cross-sectional analysis of Australian Bureau of Statistics survey data, 2017-19.

Med J Aust

To assess the socio-demographic and health-related characteristics of people who smoke daily, people who formerly smoked, and people who have never smoked in Australia.

Socio-demographic and health-related characteristics of people who smoke daily, people who formerly smoked, and people who have never smoked, expressed as population-weighted proportions, overall and by Indigeneity.

Among adult NHS respondents, an estimated 58.8% of people who smoked daily (95% confidence interval [CI], 56.2-61.4%) were men, 61.3% (95% CI, 58.7-63.9%) were 25-54 years old, 72.5% (95% CI, 70.0-74.8%) were born in Australia, and 65.4% (95% CI, 62.8-67.8%) lived in major cities and 54.3% (95% CI, 51.6-57.0%) in areas in the two socio-economically most disadvantaged quintiles; 75.9% (95% CI, 73.5-78.1%) reported good to excellent health, 73.0% (95% CI, 70.5-75.4%) reported low to moderate psychological distress, 69.0% of those aged 25-64 years (ie, of working age) had completed year 12 (high school), and 68.5% were currently employed. An estimated 2.57 million people smoke daily in Australia: 2.37 million non-Indigenous people (92%) and 195 700 Aboriginal or Torres Strait Islander people (8%).

While smoking is more frequent among people living in socio-economically disadvantaged areas and in certain population sub-groups, this first quantitative national profile indicates that most people who smoke daily are in paid employment, are non-Indigenous, are in good physical and mental health, and have completed year 12. Improved comprehensive structural supply- and demand-based tobacco control, informed by the needs of priority groups and the overall profile of people who smoke, is needed to reduce daily smoking prevalence among adults to the 2030 targets of 5% or less for all Australians and 27% or less for Aboriginal and Torres Strait Islander people.