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American Journal of Critical Care : An... Jul 2024Continuous electrocardiographic (ECG) monitoring was first introduced into hospitals in the 1960s, initially into critical care, as bedside monitors, and eventually into...
Continuous electrocardiographic (ECG) monitoring was first introduced into hospitals in the 1960s, initially into critical care, as bedside monitors, and eventually into step-down units with telemetry capabilities. Although the initial use was rather simplistic (ie, heart rate and rhythm assessment), the capabilities of these devices and associated physiologic (vital sign) monitors have expanded considerably. Current bedside monitors now include sophisticated ECG software designed to identify myocardial ischemia (ie, ST-segment monitoring), QT-interval prolongation, and a myriad of other cardiac arrhythmia types. Physiologic monitoring has had similar advances from noninvasive assessment of core vital signs (blood pressure, respiratory rate, oxygen saturation) to invasive monitoring including arterial blood pressure, temperature, central venous pressure, intracranial pressure, carbon dioxide, and many others. The benefit of these monitoring devices is that continuous and real-time information is displayed and can be configured to alarm to alert nurses to a change in a patient's condition. I think it is fair to say that critical and high-acuity care nurses see these devices as having a positive impact in patient care. However, this enthusiasm has been somewhat dampened in the past decade by research highlighting the shortcomings and unanticipated consequences of these devices, namely alarm and alert fatigue. In this article, which is associated with the American Association of Critical-Care Nurses' Distinguished Research Lecture, I describe my 36-year journey from a clinical nurse to nurse scientist and the trajectory of my program of research focused primarily on ECG and physiologic monitoring. Specifically, I discuss the good, the not so good, and the untapped potential of these monitoring systems in clinical care. I also describe my experiences with community-based research in patients with acute coronary syndrome and/or heart failure.
Topics: Humans; Electrocardiography; Monitoring, Physiologic
PubMed: 38945816
DOI: 10.4037/ajcc2024781 -
International Journal of Infectious... Jun 2024Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection (ALRI) in young children. With substantial advances in RSV research, we aimed...
OBJECTIVES
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection (ALRI) in young children. With substantial advances in RSV research, we aimed to conduct an updated systematic review of risk factors for RSV-ALRI in children under five years.
METHODS
We updated our previously published literature search to November 2022 among three English databases and additionally searched three Chinese databases (from January 1995) to identify all relevant publications. We performed random-effects meta-analyses to estimate the pooled odds ratio and 95% confidence interval (CI) for each risk factor and each outcome (RSV-ALRI in the community and RSV-ALRI hospitalisation).
RESULTS
A total of 47 studies were included (26 from the updated search). Indoor air pollution was identified as a possible risk factor for RSV-ALRI in the community (OR 1.45, 95% CI: 1.10-1.90). The identified risk factors for RSV-ALRI hospitalisation fall into four categories: demographic (male sex, Māori and Pacific ethnicities vs European or other ethnicities), pre- and post- neonatal (prematurity, low birth weight, small for gestational age, maternal smoking during pregnancy or lactation, maternal age <30 years vs 30-34 years, multiparity, caesarean section vs vaginal), household and environmental (having siblings, passive smoking, maternal asthma, daycare centre attendance), and health and medical conditions (any chronic diseases, bronchopulmonary dysplasia, HIV infections, congenital heart disease, Down syndrome, cystic fibrosis, previous asthma). The pooled ORs ranged from 1.14 to 4.55.
CONCLUSIONS
Our findings on the risk factors for RSV-ALRI help identify RSV high-risk groups, which has important implications for RSV prevention at both individual and population levels.
PubMed: 38945430
DOI: 10.1016/j.ijid.2024.107125 -
Nature Communications Jun 2024Individuals with Down syndrome, the genetic condition caused by trisomy 21, exhibit strong inter-individual variability in terms of developmental phenotypes and...
Individuals with Down syndrome, the genetic condition caused by trisomy 21, exhibit strong inter-individual variability in terms of developmental phenotypes and diagnosis of co-occurring conditions. The mechanisms underlying this variable developmental and clinical presentation await elucidation. We report an investigation of human chromosome 21 gene overexpression in hundreds of research participants with Down syndrome, which led to the identification of two major subsets of co-expressed genes. Using clustering analyses, we identified three main molecular subtypes of trisomy 21, based on differential overexpression patterns of chromosome 21 genes. We subsequently performed multiomics comparative analyses among subtypes using whole blood transcriptomes, plasma proteomes and metabolomes, and immune cell profiles. These efforts revealed strong heterogeneity in dysregulation of key pathophysiological processes across the three subtypes, underscored by differential multiomics signatures related to inflammation, immunity, cell growth and proliferation, and metabolism. We also observed distinct patterns of immune cell changes across subtypes. These findings provide insights into the molecular heterogeneity of trisomy 21 and lay the foundation for the development of personalized medicine approaches for the clinical management of Down syndrome.
Topics: Down Syndrome; Humans; Chromosomes, Human, Pair 21; Female; Transcriptome; Male; Child; Child, Preschool; Adult; Gene Expression Profiling; Proteome; Adolescent
PubMed: 38942750
DOI: 10.1038/s41467-024-49781-1 -
Aging Jun 2024Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress...
Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and a dementia onset resembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). Our results show that DS mice show increased liver oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Therefore, DS liver exhibits an altered inflammatory response and mitochondrial fitness as we showed by assaying the expression of HMOX1, CLPP, and the heat shock proteins Hsp90 and Hsp60. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of PPARα, PPARγ, FATP5, and CTP2. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Consistently, histological analysis of DS liver reveals increased fibrosis and steatosis, as showed by Col1a1 increased expression, indicative of potential progression to liver cirrhosis. Therefore, our findings suggest an increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed a light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.
PubMed: 38942607
DOI: 10.18632/aging.205970 -
Human Reproduction (Oxford, England) Jun 2024Can pregnancy outcomes following fresh elective single embryo transfer (eSET) in gonadotropin-releasing hormone (GnRH) antagonist protocols increase using a gonadotropin...
A modified flexible GnRH antagonist protocol using antagonist early cessation and a gonadotropin step-down approach improves live birth rates in fresh cycles: a randomized controlled trial.
STUDY QUESTION
Can pregnancy outcomes following fresh elective single embryo transfer (eSET) in gonadotropin-releasing hormone (GnRH) antagonist protocols increase using a gonadotropin (Gn) step-down approach with cessation of GnRH antagonist on the day of hCG administration (hCG day) in patients with normal ovarian response?
SUMMARY ANSWER
The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on the hCG day is effective in improving live birth rates (LBRs) per fresh eSET cycle.
WHAT IS KNOWN ALREADY
Currently, there is no consensus on optimal GnRH antagonist regimens. Studies have shown that fresh GnRH antagonist cycles result in poorer pregnancy outcomes than the long GnRH agonist (GnRHa) protocol. Endometrial receptivity is a key factor that contributes to this phenomenon.
STUDY DESIGN, SIZE, DURATION
An open label randomized controlled trial (RCT) was performed between November 2021 and August 2022. There were 546 patients allocated to either the modified GnRH antagonist or the conventional antagonist protocol at a 1:1 ratio.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Both IVF and ICSI cycles were included, and the sperm samples used were either fresh or frozen from the partner, or from frozen donor ejaculates. The primary outcome was the LBRs per fresh SET cycle. Secondary outcomes included rates of implantation, clinical and ongoing pregnancy, miscarriage, and ovarian hyperstimulation syndrome (OHSS), as well as clinical outcomes of ovarian stimulation.
MAIN RESULTS AND THE ROLE OF CHANCE
Baseline demographic features were not significantly different between the two ovarian stimulation groups. However, in the intention-to-treat (ITT) population, the LBRs in the modified antagonist group were significantly higher than in the conventional group (38.1% [104/273] vs. 27.5% [75/273], relative risk 1.39 [95% CI, 1.09-1.77], P = 0.008). Using a per-protocol (PP) analysis which included all the patients who received an embryo transfer, the LBRs in the modified antagonist group were also significantly higher than in the conventional group (48.6% [103/212] vs. 36.8% [74/201], relative risk 1.32 [95% CI, 1.05-1.66], P = 0.016). The modified antagonist group achieved significantly higher implantation rates, and clinical and ongoing pregnancy rates than the conventional group in both the ITT and PP analyses (P < 0.05). The two groups did not show significant differences between the number of oocytes retrieved or mature oocytes, two-pronuclear zygote (2PN) rates, the number of embryos obtained, blastocyst progression and good-quality embryo rates, early miscarriage rates, or OHSS incidence rates (P > 0.05).
LIMITATIONS, REASONS FOR CAUTION
A limitation of our study was that the subjects were not blinded to the treatment allocation in the RCT trial. Only women under 40 years of age who had a good prognosis were included in the analysis. Therefore, use of the modified antagonist protocol in older patients with a low ovarian reserve remains to be investigated. In addition, the sample size for Day 5 elective SET was small, so larger trials will be required to strengthen these findings.
WIDER IMPLICATIONS OF THE FINDINGS
The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on hCG day improved the LBRs per fresh eSET cycle in normal responders.
STUDY FUNDING/COMPETING INTEREST(S)
This project was funded by grant 2022YFC2702503 from the National Key Research & Development Program of China and grant 2021140 from the Beijing Health Promotion Association. The authors declare no conflicts of interest.
TRIAL REGISTRATION NUMBER
The RCT was registered in the Chinese Clinical Trial Registry; Study Number: ChiCTR2100053453.
TRIAL REGISTRATION DATE
21 November 2021.
DATE OF FIRST PATIENT’S ENROLLMENT
23 November 2021.
PubMed: 38942602
DOI: 10.1093/humrep/deae145 -
Alzheimer's & Dementia : the Journal of... Jun 2024Trisomy 21, or Down syndrome (DS), predisposes individuals to early-onset Alzheimer's disease (AD). While monoclonal antibodies (mAbs) targeting amyloid are approved for...
INTRODUCTION
Trisomy 21, or Down syndrome (DS), predisposes individuals to early-onset Alzheimer's disease (AD). While monoclonal antibodies (mAbs) targeting amyloid are approved for older AD patients, their efficacy in DS remains unexplored. This study examines amyloid positron emission tomography (PET) positivity (A+), memory function, and clinical status across ages in DS to guide mAb trial designs.
METHODS
Cross-sectional data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS) was analyzed. PET amyloid beta in Centiloids classified amyloid status using various cutoffs. Episodic memory was assessed using the modified Cued Recall Test, and clinical status was determined through consensus processes.
RESULTS
Four hundred nine DS adults (mean age = 44.83 years) were evaluated. A+ rates increased with age, with mean amyloid load rising significantly. Memory decline and cognitive impairment are also correlated with age.
DISCUSSION
These findings emphasize the necessity of tailoring mAb trials for DS, considering age-related AD characteristics.
HIGHLIGHTS
There is rapid increase in prevalence of amyloid beta (Aβ) positron emission tomography (PET) positivity in Down syndrome (DS) after the age of 40 years. Aβ PET positivity thresholds have significant impact on prevalence rates in DS. There is a significant lag between Aβ PET positivity and clinical symptom onset in DS.
PubMed: 38940611
DOI: 10.1002/alz.14068 -
Cytometry. Part B, Clinical Cytometry Jun 2024Hematologic neoplasms with germline predisposition have been increasingly recognized as a distinct category of tumors over the last few years. As such, this category was... (Review)
Review
Hematologic neoplasms with germline predisposition have been increasingly recognized as a distinct category of tumors over the last few years. As such, this category was added to the World Health Organization (WHO) 4th edition as well as maintained in the WHO 5th edition and International Consensus Classification (ICC) 2022 classification systems. In practice, these tumors require a high index of suspicion and confirmation by molecular testing. Flow cytometry is a cost-effective diagnostic tool that is routinely performed on peripheral blood and bone marrow samples. In this review, we sought to summarize the current body of research correlating flow cytometric immunophenotype to assess its utility in diagnosis of and clinical decision making in germline hematologic neoplasms. We also illustrate these findings using cases mostly from our own institution. We review some of the more commonly mutated genes, including CEBPA, DDX41, RUNX1, ANKRD26, GATA2, Fanconi anemia, Noonan syndrome, and Down syndrome. We highlight that flow cytometry may have a role in the diagnosis (GATA2, Down syndrome) and screening (CEBPA) of some germline predisposition syndromes, although appears to show nonspecific findings in others (DDX41, RUNX1). In many of the others, such as ANKRD26, Fanconi anemia, and Noonan syndrome, further studies are needed to better understand whether specific flow cytometric patterns are observed. Ultimately, we conclude that further studies such as large case series and organized data pipelines are needed in most germline settings to better understand the flow cytometric immunophenotype of these neoplasms.
PubMed: 38940080
DOI: 10.1002/cyto.b.22192 -
Cureus May 2024Prenatal screening tests are essential for preventing common genetic disorders, yet their acceptability among pregnant women in India remains unexplored. This study aims...
INTRODUCTION
Prenatal screening tests are essential for preventing common genetic disorders, yet their acceptability among pregnant women in India remains unexplored. This study aims to investigate the acceptability of prenatal screening tests and their correlation with demographic characteristics among pregnant women in India.
METHODS
A cross-sectional study was conducted at a tertiary care, public hospital, involving 200 pregnant women. Data were collected through a self-administered questionnaire assessing demographic information and the acceptability of prenatal screening tests. Statistical analysis included chi-square tests and logistic regression.
RESULTS
Most participants demonstrated adequate acceptability toward prenatal screening tests, with 73% scoring above the threshold. Factors associated with higher acceptability included younger maternal age, second-trimester gestational age, higher education, salaried employment, and urban residence. However, factors such as parity, consanguinity, mode of conception, and family history of genetic disease showed no significant associations.
CONCLUSION
The study highlights positive attitudes toward prenatal screening tests among pregnant women in India, particularly among younger, more educated, and urban populations. These findings emphasize the need for targeted interventions to enhance awareness and accessibility of prenatal screening, ultimately contributing to the reduction of the genetic disorder burden in India.
PubMed: 38939276
DOI: 10.7759/cureus.61246 -
JACC. Advances Nov 2023
PubMed: 38938705
DOI: 10.1016/j.jacadv.2023.100673 -
Thorax Jun 2024In adults and children with intellectual disability (ID), sleep -disordered breathing (SDB) is thought to be common. However, large epidemiological studies are lacking,... (Review)
Review
BACKGROUND
In adults and children with intellectual disability (ID), sleep -disordered breathing (SDB) is thought to be common. However, large epidemiological studies are lacking, and there are few studies on optimal methods of investigation and even fewer randomised, controlled intervention trials of treatment.
METHOD
Peer-reviewed publications from various databases were examined in line with search terms relevant to ID and SDB spanning the years 200-2024.
RESULTS
Findings suggest that, due to comorbid conditions, children and adults with ID may experience both an increased risk of SDB, as well as lower frequency of diagnosis. SDB can compromise the emotional, physical and mental health of individuals with ID. Appropriate treatment when tolerated leads to an improvement in health and well-being and several studies emphasized the importance of consistent follow-up of people with ID - something that is not universally occurring during childhood, in the transition to adulthood and during adulthood itself. As the most frequently occurring form of ID worldwide, we use Down syndrome as a specific example of how diagnosing and treating SDB can lead to improved outcomes.
CONCLUSIONS
This review highlights the importance of identifying SDB in this heterogenous population, recognising the multi-faceted, deleterious consequences of untreated SDB in people with ID, and presents some strategies that can be harnessed to improve diagnosis and management. Until further ID-specific research is available, we urge flexibility in the approach to people with ID and SDB based in guidelines and standard practice developed for the typically developing population.
PubMed: 38937106
DOI: 10.1136/thorax-2023-220032