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Vaccine Jan 2024In 2021, thrombosis with thrombocytopenia syndrome (TTS) was confirmed by the European Medicines Agency (EMA) as a rare side effect of the COVID-19 adenovirus vector...
Public's perspective on COVID-19 adenovirus vector vaccines after thrombosis with thrombocytopenia syndrome (TTS) reports and associated regulatory actions - A cross-sectional study in six EU member states.
OBJECTIVE
In 2021, thrombosis with thrombocytopenia syndrome (TTS) was confirmed by the European Medicines Agency (EMA) as a rare side effect of the COVID-19 adenovirus vector vaccines Vaxzevria® and Jcovden®. This study aimed to describe the public's knowledge of TTS and how it affected the willingness to be vaccinated with COVID-19 vaccines and other vaccines in six European countries.
METHODS
From June to October of 2022, a multi-country cross-sectional online survey was conducted in Denmark, Greece, Latvia, Netherlands, Portugal, and Slovenia. The minimum target of participants to be recruited was based on the size of the country's population. The results were analysed descriptively.
RESULTS
In total, 3794 respondents were included in the analysis; across the six countries, 33.3 %-68.3 % reported being familiar with signs and symptoms of TTS, although 3.1-61.4 % of those were able to identify the symptoms correctly. The reported changes in willingness to be vaccinated against COVID-19 and with other vaccines varied per country. The largest reported change in the willingness to be vaccinated with Vaxzevria® and Jcovden® was observed in Denmark (61.2 %), while the willingness to be vaccinated with other COVID-19 vaccines changed most in Slovenia (30.4 %). The smallest decrease in willingness towards future vaccination against COVID-19 was reported in the Netherlands (20.9 %) contrasting with the largest decrease observed in Latvia (69.1 %).
CONCLUSION
Knowledge about TTS seemed to have influenced the public's opinion in Europe resulting in less willingness to be vaccinated with Vaxzevria® and Jcovden®. Willingness for vaccination against COVID-19 with other vaccines and widespread use of vaccines to prevent other diseases also differed and seemed to be determined by the approaches taken by national health authorities when reacting to and communicating about COVID-19 vaccination risks. Further investigation of optimal risk communication strategies is warranted.
Topics: Humans; COVID-19 Vaccines; Cross-Sectional Studies; COVID-19; ChAdOx1 nCoV-19; Vaccination; Thrombocytopenia; Adenoviridae; Thrombosis
PubMed: 38182460
DOI: 10.1016/j.vaccine.2023.12.065 -
Epigenetics Dec 2024Currently, clinicians use their judgement and indices such as the Prediction of Alcohol Withdrawal Syndrome Scale (PAWSS) to determine whether patients are admitted to...
Currently, clinicians use their judgement and indices such as the Prediction of Alcohol Withdrawal Syndrome Scale (PAWSS) to determine whether patients are admitted to hospitals for consideration of withdrawal syndrome (AWS). However, only a fraction of those admitted will experience severe AWS. Previously, we and others have shown that epigenetic indices, such as the Alcohol T-Score (ATS), can quantify recent alcohol consumption. However, whether these or other alcohol biomarkers, such as carbohydrate deficient transferrin (CDT), could identify those at risk for severe AWS is unknown. To determine this, we first conducted genome-wide DNA methylation analyses of subjects entering and exiting alcohol treatment to identify loci whose methylation quickly reverted as a function of abstinence. We then tested whether methylation at a rapidly reverting locus, cg07375256, or other existing metrics including PAWSS scores, CDT levels, or ATS, could predict outcome in 125 subjects admitted for consideration of AWS. We found that PAWSS did not significantly predict severe AWS nor seizures. However, methylation at cg07375256 () and CDT strongly predicted severe AWS with ATS ( < 0.007) and cg07375256 ( < 6 × 10-5) methylation also predicting AWS associated seizures. We conclude that epigenetic methods can predict those likely to experience severe AWS and that the use of these or similar Precision Epigenetic approaches could better guide AWS management.
Topics: Humans; Alcoholism; DNA Methylation; Ethanol; Seizures; Substance Withdrawal Syndrome; Zinc Fingers
PubMed: 38166538
DOI: 10.1080/15592294.2023.2298057 -
MedRxiv : the Preprint Server For... Dec 2023Infants with complex congenital heart disease (CHD) require life-saving corrective/palliative heart surgery in the first weeks of life. These infants are at risk for...
BACKGROUND
Infants with complex congenital heart disease (CHD) require life-saving corrective/palliative heart surgery in the first weeks of life. These infants are at risk for brain injury and poor neurodevelopmental outcomes. Cerebral microhemorrhages (CMH) are frequently seen after neonatal bypass heart surgery, but it remains unknown if CMH are a benign finding or constitute injury. Herein, we investigate the risk factors for developing CMH and their clinical significance.
METHODS
192 infants with CHD undergoing corrective cardiac surgery with cardiopulmonary bypass (CPB) at a single institution were prospectively evaluated with pre-(n = 183) and/or postoperative (n = 162) brain magnetic resonance imaging (MRI). CMH severity was scored based on total number of microhemorrhages. Antenatal, perioperative, and postoperative candidate risk factors for CMH and neurodevelopmental (ND) outcomes were analyzed. Eighteen-month neurodevelopmental outcomes were assessed using the Bayley-III Scales of Infants and Toddler Development in a subset of patients (n = 82). Linear regression was used to analyze associations between risk factors or ND outcomes and presence/number of CMH.
RESULTS
The most common CHD subtypes were hypoplastic left heart syndrome (HLHS) (37%) and transposition of the great arteries (TGA) (33%). Forty-two infants (23%) had CMH present on MRI before surgery and 137 infants (85%) post-surgery. No parameters evaluated were significant risk factors for preoperative CMH. In multivariate analysis, cardiopulmonary bypass (CPB) duration (p < 0.0001), use of extracorporeal membrane oxygenation (ECMO) support (p < 0.0005), postoperative seizure(s) (p < 0.03), and lower birth weight (p < 0.03) were associated with new or worsened CMH postoperatively. Higher CMH number was associated with lower scores on motor (p < 0.03) testing at 18 months.
CONCLUSION
CMH is a common imaging finding in infants with CHD with increased prevalence and severity after CPB and adverse impact on neurodevelopmental outcomes starting at a young age. Longer duration of CPB and need for postoperative ECMO were the most significant risk factors for developing CMH. However, presence of CMH on preoperative scans indicates non-surgical risk factors that are yet to be identified. Neuroprotective strategies to mitigate risk factors for CMH may improve neurodevelopmental outcomes in this vulnerable population.
PubMed: 38105980
DOI: 10.1101/2023.12.05.23299539 -
Scientific Reports Dec 2023Characterization of the pathophysiology of ARDS following chlorine gas inhalation in clinically relevant translational large animal models is essential, as the...
Characterization of the pathophysiology of ARDS following chlorine gas inhalation in clinically relevant translational large animal models is essential, as the opportunity for clinical trials in this type of trauma is extremely limited. To investigate Cl concentration and gender-dependent ARDS severity. Sheep (n = 54) were exposed to air or Cl premixed in air at a concentration of 50, 100, 200, and 300 ppm for 30 min under anesthesia/analgesia and monitored for an additional 48 h in a conscious state. Cardiopulmonary variables and survival endpoints were compared between male and female sheep. Overall there were no significant differences in the responses of female and male sheep except pulmonary oxygenation tended to be better in the male sheep (300 ppm group), and the pulmonary arterial pressure was lower (200 ppm group). The onset of mild ARDS (200 < PaO/FiO ≤ 300) was observed at 36 h post exposure in the 50 ppm group, whereas the 100 ppm group developed mild and moderate (100 ≤ PaO/FiO ≤ 200) ARDS by 12 and 36 h after injury, respectively. The 200 ppm and 300 ppm groups developed moderate ARDS within 6 and 3 h after injury, respectively. The 300 ppm group progressed to severe (PaO/FiO ≤ 100) ARDS at 18 h after injury. Increases in pPeak and pPlateau were noted in all injured animals. Compared to sham, inhalation of 200 ppm and 300 ppm Cl significantly increased lung extravascular water content. The thoracic cavity fluid accumulation dose-dependently increased with the severity of trauma as compared to sham. At necropsy, the lungs were red, heavy, solidified, and fluid filled; the injury severity grew with increasing Cl concentration. The severity of ARDS and mortality rate directly correlated to inhaled Cl concentrations. No significant sex-dependent differences were found in measured endpoint variables.
Topics: Male; Female; Animals; Sheep; Chlorine; Lung; Administration, Inhalation; Respiratory Distress Syndrome
PubMed: 38102196
DOI: 10.1038/s41598-023-48720-2 -
Clinical Infectious Diseases : An... Apr 2024Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active...
BACKGROUND
Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear.
METHODS
We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality.
RESULTS
CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10-6.19] and 2.03 [95% CI 1.24-3.33], respectively). CD4 cell counts below 350 cells/μL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies.
CONCLUSIONS
In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM.
Topics: Humans; Acquired Immunodeficiency Syndrome; HIV; HIV Infections; Anti-Retroviral Agents; CD4 Lymphocyte Count; Neoplasms; CD4-CD8 Ratio; Viral Load; Anti-HIV Agents
PubMed: 38092042
DOI: 10.1093/cid/ciad671 -
BMC Pulmonary Medicine Dec 2023Usual Interstitial Pneumonia (UIP) is characterized by progression of lung parenchyma that may be observed in various autoimmune rheumatic diseases (ARDs), including... (Review)
Review
Usual Interstitial Pneumonia (UIP) is characterized by progression of lung parenchyma that may be observed in various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis and connective tissue diseases. From a diagnostic point of view, a UIP pattern related to ARDs may display imaging and pathological features able to distinguish it from that related to IPF, such as the "straight-edge" sign at HRCT and lymphoplasmacytic infiltrates at histologic specimens. Multidisciplinary approach (MDD), involving at least pulmonologist, rheumatologist and radiologist, is fundamental in the differential diagnosis process, but MDD is also required in the evaluation of severity, progression and response to treatment, that is based on the combination of changes in symptoms, pulmonary function trends, and, in selected patients, serial CT evaluation. Differently from IPF, in patients with ARDs both functional evaluation and patient-reported outcomes may be affected by systemic involvement and comorbidities, including musculoskeletal manifestations of disease. Finally, in regards to pharmacological treatment, immunosuppressants have been considered the cornerstone of therapy, despite the lack of solid evidence in most cases; recently, antifibrotic drugs were also proposed for the treatment of progressive fibrosing ILDs other than IPF. In ARD-ILD, the therapeutic choice should balance the need for the control of systemic and lung involvements with the risk of adverse events from multi-morbidities and -therapies. Purpose of this review is to summarize the definition, the radiological and morphological features of the UIP pattern in ARDs, together with risk factors, diagnostic criteria, prognostic evaluation, monitoring and management approaches of the UIP-ARDs.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung; Autoimmune Diseases; Rheumatic Diseases; Respiratory Distress Syndrome
PubMed: 38082233
DOI: 10.1186/s12890-023-02783-z -
Endocrine Connections Feb 2024Endometriosis and polycystic ovary syndrome (PCOS) are common gynecological disorders that constitute a significant burden of disease in women of fertile age. The... (Review)
Review
Endometriosis and polycystic ovary syndrome (PCOS) are common gynecological disorders that constitute a significant burden of disease in women of fertile age. The disorders share a link to female reproduction and infertility; however, divergent effects on menstrual cycle, related hormones, and body composition have been proposed. Disorders of the thyroid gland including abnormal thyroid dysfunction (hyperthyroidism or hypothyroidism) and/or markers of thyroid autoimmunity similarly show a female predominance and onset in younger age groups. We reviewed the literature on the association between endometriosis, PCOS, and thyroid disease up until July 1, 2023, and identified 8 original studies on endometriosis and thyroid disease and 30 original studies on PCOS and thyroid disease. The studies were observational and heterogeneous regarding the design, sample size, and definitions of exposure and outcome; however, a tendency was seen toward an association between hyperthyroidism and endometriosis. Especially an association between endometriosis and slightly elevated levels of thyroid-stimulating hormone receptor antibodies has been found and corroborated in studies from different populations. On the other hand, the literature review turned a focus toward an association between hypothyroidism and PCOS, however, with uncertainties as to whether the association is caused by hypothyroidism per se and/or the thyroid autoantibodies (thyroid peroxidase and thyroglobulin antibodies). More evidence is needed to substantiate an association between endometriosis, PCOS, and thyroid disease, and to differentiate between the role of thyroid function and thyroid autoimmunity. Furthermore, studies are warranted to extend knowledge on the different disease characteristics and underlying mechanisms.
PubMed: 38078917
DOI: 10.1530/EC-23-0431 -
PNAS Nexus Dec 2023Immunocompromised patients often fail to raise protective vaccine-induced immunity against the global emergence of severe acute respiratory syndrome coronavirus 2...
Immunocompromised patients often fail to raise protective vaccine-induced immunity against the global emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Although monoclonal antibodies have been authorized for clinical use, most have lost their ability to potently neutralize the evolving Omicron subvariants. Thus, there is an urgent need for treatment strategies that can provide protection against these and emerging SARS-CoV-2 variants to prevent the development of severe coronavirus disease 2019. Here, we report on the design and characterization of a long-acting viral entry-blocking angiotensin-converting enzyme 2 (ACE2) dimeric fusion molecule. Specifically, a soluble truncated human dimeric ACE2 variant, engineered for improved binding to the receptor-binding domain of SARS-CoV-2, was fused with human albumin tailored for favorable engagement of the neonatal fragment crystallizable receptor (FcRn), which resulted in enhanced plasma half-life and allowed for needle-free transmucosal delivery upon nasal administration in human FcRn-expressing transgenic mice. Importantly, the dimeric ACE2-fused albumin demonstrated potent neutralization of SARS-CoV-2 immune escape variants.
PubMed: 38077689
DOI: 10.1093/pnasnexus/pgad403 -
The Journal of Pediatric Pharmacology... 2023We present a case of bidirectional ventricular tachycardia in a 15-year-old boy asymptomatic for arrhythmias, whose major complaint was muscle weakness. At our first...
We present a case of bidirectional ventricular tachycardia in a 15-year-old boy asymptomatic for arrhythmias, whose major complaint was muscle weakness. At our first evaluation he was receiving sotalol for his ventricular arrhythmias. In addition to bidirectional tachycardia, electrocardiogram during sinus rhythm showed prominent U waves and prolonged QT-U interval. These electrocardiographic signs, along with the evidence of clinodactyly and mild hypertelorism, led us to the diagnosis of Andersen-Tawil syndrome, confirmed by genetic analysis that revealed a "" missense mutation of KCNJ2 gene. Monotherapy with flecainide was rapidly effective and almost eliminated ventricular arrhythmias. After a 4-year follow-up there were no adverse events, flecainide has been well tolerated without significant modification of the QRS or repolarization, and ventricular arrhythmias have not been relapsed to date. The case highlights the importance of a correct clinical diagnosis, which is crucial for the optimal selection of the most appropriate drug therapy, which is expected not to be harmful, before being beneficial.
PubMed: 38025154
DOI: 10.5863/1551-6776-28.7.662 -
Therapeutic Advances in... 2023Severe mental illness (SMI) is associated with increased cardiovascular risk. Dyslipidaemia is a potentially modifiable risk factor, which may be inadequately managed in...
BACKGROUND
Severe mental illness (SMI) is associated with increased cardiovascular risk. Dyslipidaemia is a potentially modifiable risk factor, which may be inadequately managed in patients with SMI.
OBJECTIVES
To assess management of dyslipidaemia in patients with SMI healthy controls (HCs) in 2005 and 2015.
DESIGN AND METHODS
Using Danish registers, we identified adult patients with SMI in the Greater Copenhagen Area (schizophrenia spectrum disorders or bipolar disorder) with ⩾1 general practitioner contact in the year before 2005 and 2015, respectively, and HCs without SMI matched on age and gender (1:5). Outcomes were lipid-profile measurements, presence of dyslipidaemia and redemption of lipid-lowering pharmacotherapy. Differences in outcomes between patients with SMI and controls were measured with multivariable logistic regression.
RESULTS
We identified 7217 patients with SMI in 2005 and 9939 in 2015. After 10 years, patients went from having lower odds of lipid measurements to having higher odds of lipid measurements compared with HCs [odds ratio (OR) 0.70 (99% confidence interval (CI) 0.63-0.78) OR 1.34 (99% CI 1.24-1.44); < 0.01]. Patients had higher odds of dyslipidaemia during both years [OR 1.43 (99% CI 1.10-1.85) and OR 1.23 (99% CI 1.08-1.41)]. Patients went from having lower odds of receiving lipid-lowering pharmacotherapy to having higher odds of receiving lipid-lowering pharmacotherapy [OR 0.77 (99% CI 0.66-0.89) OR 1.37 (99% CI 1.24-1.51); < 0.01]. However, among persons at high cardiovascular risk, patients had lower odds of receiving lipid-lowering pharmacotherapy during both years, including subsets with previous acute coronary syndrome [OR 0.30 (99% CI 0.15-0.59) and OR 0.44 (99% CI 0.24-0.83)] and ischaemic stroke or transient ischaemic attack (TIA) [OR 0.43 (99% CI 0.26-0.69) and OR 0.61 (99% CI 0.41-0.89)].
CONCLUSION
These results imply an increased general awareness of managing dyslipidaemia among patients with SMI in the primary prophylaxis of cardiovascular disease. However, secondary prevention with lipid-lowering drugs in patients with SMI at high cardiovascular risk may be lacking.
PubMed: 38022836
DOI: 10.1177/20451253231211574