BACKGROUND: Postoperative nausea and vomiting (PONV) in pediatric patients is a common and clinically significant postoperative complication. The incidence of PONV has not been extensively studied in large pediatric cohorts. Furthermore, in 2020, the Fourth Consensus Guidelines for the management of PONV were published. However, the association between perioperative factors and adherence to these guidelines remains unclear. This study aims to assess both the incidence of PONV and guideline adherence within a large and diverse pediatric population. METHODS: We conducted a retrospective observational study at a large tertiary medical center, including pediatric patients (≤18 years) who underwent surgery between September 2020 and March 2023. We conducted a retrospective analysis of data from our electronic health records, focusing on patient demographics, surgical details, anesthesia details, and prophylaxis for PONV. We calculated the incidence of PONV and used multivariable logistic regression to identify the predictors of guideline adherence. RESULTS: The cohort included 3772 patients with a median (interquartile range [IQR]) age of 9.21 (3.55-14.68) years. The incidence (95% confidence intervals) of early PONV was 1.0% (0.7-1.4) and 3.8% (3.2-4.5) for delayed PONV. Adherence to the fourth consensus guidelines for PONV management was observed in 32.5% (31.0-34.0) of cases. A high risk of PONV was identified in 55.9% (54.3-57.5) of the patients. The most common number of PONV risk factors was 3, observed in 1151 patients (30.5% [29.1-32.0]). Significant predictors of guideline adherence included the intraoperative use of long-acting opioids (odds ratio [OR], 2.711, P < .001) and age ≥3 years (OR, 2.074, P < .001). Nonadherence was associated with a higher incidence of PONV at 24 hours postsurgery (4.4% (3.6-5.2) vs 2.7% (1.9-3.8), P = .012). Factors such as specific high PONV risk surgeries ( P = .001), maintenance with inhalational agents solely ( P = .017), and neostigmine use ( P < .001) were also all statistically significant. CONCLUSIONS: Our study revealed a lower-than-expected incidence of PONV in pediatric patients, highlighting the need for standardized definitions and improved reporting. Adherence to PONV guidelines was suboptimal, emphasizing the need for better implementation strategies.
- MeSH
- Antiemetics therapeutic use MeSH
- Child MeSH
- Guideline Adherence * standards MeSH
- Incidence MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Postoperative Nausea and Vomiting * epidemiology diagnosis prevention & control MeSH
- Child, Preschool MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Practice Guidelines as Topic standards MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
OBJECTIVE: Research suggests that disrupted interoception contributes to the development and maintenance of functional neurological disorder (FND); however, no functional neuroimaging studies have examined the processing of interoceptive signals in patients with FND. METHODS: The authors examined univariate and multivariate functional MRI neural responses of 38 patients with mixed FND and 38 healthy control individuals (HCs) during a task exploring goal-directed attention to cardiac interoception-versus-control (exteroception or rest) conditions. The relationships between interoception-related neural responses, heartbeat-counting accuracy, and interoceptive trait prediction error (ITPE) were also investigated for FND patients. RESULTS: When attention was directed to heartbeat signals versus exteroception or rest tasks, FND patients showed decreased neural activations (and reduced coactivations) in the right anterior insula and bilateral dorsal anterior cingulate cortices (among other areas), compared with HCs. For FND patients, heartbeat-counting accuracy was positively correlated with right anterior insula and ventromedial prefrontal activations during interoception versus rest. Cardiac interoceptive accuracy was also correlated with bilateral dorsal anterior cingulate activations in the interoception-versus-exteroception contrast, and neural activations were correlated with ITPE scores, showing inverse relationships to those observed for heartbeat-counting accuracy. CONCLUSIONS: This study identified state and trait interoceptive disruptions in FND patients. Convergent between- and within-group findings contextualize the pathophysiological role of cingulo-insular (salience network) areas across the spectrum of functional seizures and functional movement disorder. These findings provide a starting point for the future development of comprehensive neurophysiological assessments of interoception for FND patients, features that also warrant research as potential prognostic and monitoring biomarkers.
- MeSH
- Adult MeSH
- Interoception * physiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Brain Mapping MeSH
- Young Adult MeSH
- Brain * physiopathology diagnostic imaging MeSH
- Nervous System Diseases * physiopathology diagnostic imaging MeSH
- Attention physiology MeSH
- Heart Rate physiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The safety profile of venom immunotherapy (VIT) is a relevant issue, and considerable differences have been reported in the safety and efficacy of this treatment modality. The primary aim of this study was to evaluate the safety of angiotensin-converting enzyme inhibitors and ß-blockers during VIT. In a second analysis, we evaluated data on premedication and venom preparations and their association with systemic adverse events (AEs) during the up-dosing phase and the first year of the maintenance phase, as well as the outcome of field stings and sting challenges. METHODS: Ours was an open, prospective, observational, multicenter study that recruited 1425 patients, of whom 1342 underwent VIT. RESULTS: Premedication with oral antihistamines was taken by 52.1% of patients during up-dosing and 19.7% of patients during the maintenance phase. Antihistamines had no effect on the frequency of systemic AEs (P=.11), although large local reactions (LLRs) were less frequent (OR, 0.74; 95%CI, 0.58-0.96; P=.02). Aqueous preparations were preferred for up-dosing (73.0%), and depot preparations were used for the maintenance phase (64.5%). The type of venom preparation had no influence on the frequency of systemic AEs or on the effectiveness of VIT (P=.26 and P=.80, respectively), while LLRs were less frequent with depot preparations (P<.001). CONCLUSIONS: Pretreatment with oral antihistamines during VIT significantly reduces the frequency of LLRs but not systemic AEs. All venom preparations were equally effective and did not differ in terms of the frequency of systemic AEs.
- MeSH
- Allergens immunology administration & dosage MeSH
- Histamine Antagonists therapeutic use MeSH
- Adrenergic beta-Antagonists therapeutic use MeSH
- Desensitization, Immunologic * methods adverse effects MeSH
- Child MeSH
- Adult MeSH
- Angiotensin-Converting Enzyme Inhibitors therapeutic use adverse effects MeSH
- Insect Bites and Stings immunology MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Prospective Studies MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Venoms immunology adverse effects therapeutic use MeSH
- Animals MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Observational Study MeSH
INTRODUCTION/AIMS: Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care. METHODS: Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs). RESULTS: The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death. DISCUSSION: Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.
- MeSH
- Autoantibodies blood MeSH
- Activities of Daily Living MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Immunologic Factors therapeutic use adverse effects administration & dosage MeSH
- Immunoglobulins, Intravenous * therapeutic use adverse effects administration & dosage MeSH
- Middle Aged MeSH
- Humans MeSH
- Myasthenia Gravis * drug therapy MeSH
- Prospective Studies MeSH
- Receptors, Cholinergic * immunology MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase II MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
Obezita je chronické, relabující a progredující onemocnění s rostoucí prevalencí, které významně ovlivňuje zdraví a kvalitu života i u dětí. Je spojena se zvýšeným rizikem metabolických a kardiovaskulárních onemocnění, jako je inzulinová rezistence, diabetes mellitus 2. typu, hypertenze, dyslipidémie a metabolicky asociovaná steatóza jater. Obezita dále může vést k rozvoji syndromu spánkové apnoe, ortopedickým a psychickým komplikacím. Základem terapie je edukace zdravého životního stylu celé rodiny, která však často naráží na překážky, jako jsou časová náročnost, omezená dostupnost specialistů a nízká dlouhodobá adherence rodin. Telemedicína nabízí inovativní přístup ke zlepšení léčby obezity dětí prostřednictvím digitálních nástrojů, online konzultací, chytrých aplikací a nositelných technologií. Umožňuje efektivnější monitorování stravovacích a pohybových návyků, podporu psychického zdraví i snížení časové a finanční zátěže pro rodiny. Výsledky studií ukazují, že kombinace prezenční a distanční podpory a aktivní zapojení rodinných příslušníků vede k vyšší úspěšnosti v redukci tělesné hmotnosti a udržení zdravého životního stylu. Článek se zaměřuje na využití telemedicíny v léčbě obezity u dětí, přehled metod, které byly v této oblasti aplikovány, a jejich účinnost v kontextu současných vědeckých poznatků.
Obesity is a chronic, relapsing, and progressive disease with increasing prevalence, that significantly impacts health and quality of life, even in children. It is associated with an increased risk of metabolic and cardiovascular diseases such as insulin resistance, type 2 diabetes mellitus, hypertension, dyslipidemia, and metabolic dysfunction-associated steatotic liver disease. Additionally, obesity can lead to the development of sleep apnea syndrome, orthopedic issues, and psychological complications. The cornerstone of the care is educating the whole family about a healthy lifestyle; however, this may often be challenging due to obstacles such as time constraints, limited access to specialists, and low long-term adherence of families. Telemedicine offers an innovative approach to improving obesity treatment in children through digital tools, online consultations, smart applications, and wearable technologies. It enables more effective monitoring of dietary and physical activity habits, supports mental health, and reduces time and financial burdens for families. Studies indicate that combining in-person and remote support, along with active involvement of family members, leads to higher success rates in weight reduction and a healthy lifestyle maintenance. This article focuses on the use of telemedicine in the treatment of obesity in children, providing an overview of the methods applied in this field and their effectiveness in the context of current scientific knowledge.
- MeSH
- Child MeSH
- Humans MeSH
- Pediatric Obesity * therapy MeSH
- Motor Activity MeSH
- Psychosocial Intervention methods MeSH
- Preventive Health Services methods MeSH
- Feeding Behavior psychology MeSH
- Telemedicine * MeSH
- Life Style MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
BACKGROUND: Understanding population health trends and their key determinants is essential for planning health services and implementing effective interventions. One of these determinants may be national cultural characteristics that are related to various health outcomes and health-related behaviours. However, little is known about their potential association to overall burden of disease. Thus, this study examined whether cultural characteristics expressed by Hofstede indexes are associated with the burden of disease. METHODS: We used data from open-source databases - Hofstede's Cultural Index, the Global Burden of Diseases (GBD) and the Human Development Index (HDI). The final sample comprised 69 countries covering all the continents. The burden of disease was measured using disability-adjusted life years (DALYs), years lived with disabilities (YLD), and years of life lost (YLL). National cultural characteristics were measured using Hofstede's dimensions. Bayesian correlation analyses were conducted to assess the relationships between cultural dimensions and health outcomes, stratified by countries' HDI levels. RESULTS: In countries with a very high HDI, there was strong evidence (Bayes Factor > 10) of a positive correlation of Power distance with the total disability-adjusted life years (r = 0.448) and years of life lost (r = 0.528), and Individualism (r = 0.667) and Indulgence (r = 0.494) with years lived with disabilities. In contrast, Long-term orientation negatively correlated of with years lived with disabilities (r = -0.527) and Indulgence with disability-adjusted life years (r = -0.437) and years of life lost (r = -0.537). Further, Power distance and Indulgence were correlated with the majority of the GBD indicators and Individualism with a few GBD indicators. In countries with a high and medium HDI, strong evidence of the associations was found in only a few cases. CONCLUSION: We found a correlation between national cultural characteristics and burden of disease. Policy-makers should consider integrating cultural factors into public health strategies to better align healthcare interventions with the local population's values and behaviours. Moreover, cross-cultural research and collaboration should increase to understand how cultural influences can be used to mitigate disease burdens and improve health outcomes globally. This study also opens a potentially new research area within population health research.
OBJECTIVE: Maintenance olaparib demonstrated clinical activity for progression-free survival in patients without a germline BRCA1 and/or BRCA2 mutation (non-gBRCAm) who had platinum-sensitive relapsed ovarian cancer in the phase IIIb, open-label, single-arm, non-comparator, international OPINION trial (NCT03402841). We report final overall survival (OS; secondary endpoint), prespecified secondary endpoint updates and ad hoc OS analysis by homologous recombination deficiency (HRD) and somatic BRCAm (sBRCAm) status. METHODS: Patients with non-gBRCAm platinum-sensitive relapsed ovarian cancer, ≥2 prior lines of platinum-based chemotherapy, and in response following their last platinum-based chemotherapy received 300 mg olaparib tablets twice daily until disease progression or unacceptable toxicity. RESULTS: 279 patients were enrolled and treated. With a median follow-up in patients censored for OS of 33.1 months (data cut-off September 17, 2021), median OS was 32.7 months (95 % CI 29.5-35.3); the 24-month OS rate was 65.8 %. In ad hoc subgroup analyses, OS rates tended to be higher in patients with HRD-positive tumors; 24-month OS rates were 81.5 %, 74.2 %, 72.0 % and 55.8 % in the sBRCAm, HRD-positive including sBRCAm, HRD-positive excluding sBRCAm, and HRD-negative subgroups, respectively. Grade ≥ 3 treatment-emergent adverse events were reported in 82 patients (29.4 %), most commonly anemia (13.6 %). Overall, two cases of myelodysplastic syndrome were reported (no new cases since the primary analysis). CONCLUSION: These data provide additional evidence of olaparib as maintenance therapy in patients with non-gBRCAm platinum-sensitive relapsed ovarian cancer, with longer OS observed in those with HRD-positive tumors. The safety profile was consistent with the primary analysis and known safety profile of olaparib, with no new safety findings.
- MeSH
- Progression-Free Survival MeSH
- Adult MeSH
- Carcinoma, Ovarian Epithelial * drug therapy genetics mortality MeSH
- Phthalazines * adverse effects administration & dosage therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Recurrence, Local * drug therapy genetics MeSH
- Ovarian Neoplasms * drug therapy genetics mortality MeSH
- Poly(ADP-ribose) Polymerase Inhibitors * adverse effects administration & dosage therapeutic use MeSH
- Piperazines * adverse effects administration & dosage therapeutic use MeSH
- BRCA1 Protein genetics MeSH
- BRCA2 Protein genetics MeSH
- Aged MeSH
- Maintenance Chemotherapy MeSH
- Germ-Line Mutation MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
PURPOSE: To compare the performance of targeted temperature management (TTM) at 33 °C using intravascular (IC) vs. surface-cooling (SFC) devices after out-of-hospital cardiac arrest (OHCA). METHODS: A post hoc analysis including OHCA patients randomized to hypothermia in the TTM2-trial (NCT02908308) comparing hypothermia with normothermia. The main outcome was cooling performance, defined as the proportion of patients reaching target temperature < 33.5 °C within 4 h, time outside temperature ranges during maintenance, rewarming rate and post-TTM fever. Exploratory outcomes included survival and good functional outcome, defined as modified Rankin Scale (mRS) scores of 0-3 at 6 months, analyzed using Inverse Probability Treatment Weighting (IPTW). RESULTS: Among 930 patients randomized to hypothermia, 876 were treated with a cooling device and included in this study. Of those, 27.3% received IC devices, while 72.7% received SFC devices. The proportion reaching target temperature within 4 h was higher with IC (IC: 69.6% vs. SFC: 49.2%; p < 0.001). Temperature outside ranges during the cooling period and post-TTM fever were lower with IC compared to SFC (17.2% vs. 39.6%; p < 0.001 and 0% vs. 6.3%; p < 0.001, respectively). In the exploratory IPTW analysis, 6-month survival rates were 55.2% in the IC group and 50.2% in the SFC group (OR 1.22, 95% CI 0.89-1.68) and survival with good functional outcome at 6 months was 51.1% patients in the IC group and 44.9% in the SFC (OR 1.28, 95% CI 0.93-1.77). CONCLUSIONS: Among OHCA patients randomized to hypothermia in the TTM2 study, intravascular cooling, compared with surface cooling, was associated with better cooling performance.
- MeSH
- Cardiopulmonary Resuscitation methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Hypothermia, Induced * methods MeSH
- Treatment Outcome MeSH
- Out-of-Hospital Cardiac Arrest * therapy mortality MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
AIMS: The cardiac conduction system (CCS) is progressively specified during development by interactions among a discrete number of transcription factors (TFs) that ensure its proper patterning and the emergence of its functional properties. Meis genes encode homeodomain TFs with multiple roles in mammalian development. In humans, Meis genes associate with congenital cardiac malformations and alterations of cardiac electrical activity; however, the basis for these alterations has not been established. Here, we studied the role of Meis TFs in cardiomyocyte development and function during mouse development and adult life. METHODS AND RESULTS: We studied Meis1 and Meis2 conditional deletion mouse models that allowed cardiomyocyte-specific elimination of Meis function during development and inducible elimination of Meis function in cardiomyocytes of the adult CCS. We studied cardiac anatomy, contractility, and conduction. We report that Meis factors are global regulators of cardiac conduction, with a predominant role in the CCS. While constitutive Meis deletion in cardiomyocytes led to congenital malformations of the arterial pole and atria, as well as defects in ventricular conduction, Meis elimination in cardiomyocytes of the adult CCS produced sinus node dysfunction and delayed atrio-ventricular conduction. Molecular analyses unravelled Meis-controlled molecular pathways associated with these defects. Finally, we studied in transgenic mice the activity of a Meis1 human enhancer related to an single-nucleotide polymorphism (SNP) associated by Genome-wide association studies (GWAS) to PR (P and R waves of the electrocardiogram) elongation and found that the transgene drives expression in components of the atrio-ventricular conduction system. CONCLUSION: Our study identifies Meis TFs as essential regulators of the establishment of cardiac conduction function during development and its maintenance during adult life. In addition, we generated animal models and identified molecular alterations that will ease the study of Meis-associated conduction defects and congenital malformations in humans.
- MeSH
- Action Potentials MeSH
- Phenotype MeSH
- Homeodomain Proteins * genetics metabolism MeSH
- Myocytes, Cardiac * metabolism pathology MeSH
- Myocardial Contraction MeSH
- Mice, Knockout MeSH
- Sinoatrial Node metabolism physiopathology MeSH
- Heart Conduction System * metabolism physiopathology growth & development MeSH
- Arrhythmias, Cardiac physiopathology metabolism genetics MeSH
- Heart Rate * MeSH
- Myeloid Ecotropic Viral Integration Site 1 Protein * genetics metabolism deficiency MeSH
- Age Factors MeSH
- Heart Defects, Congenital metabolism genetics physiopathology MeSH
- Gene Expression Regulation, Developmental MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH