Background: β-blockers are first-line therapy in patients with long QT syndrome (LQTS). However, β-blockers had genotype dependent efficacy (LQT1>LQT2>LQT3). Sodium channel blockers have been recommended as add-on therapy for LQT3 patients. However, the effect of sodium channel blockers in all LQT patients remains unknown. Methods: We conducted a systematic electronic search of PubMed, Embase and the Cochrane Library. Fixed effects model was used to assess the effect of sodium channel blockers on QTc, cardiac events (CEs), and the proportion of QTc≥500 ms and QTc≤460 ms in LQTS patients. Results: Pooled analysis of 14 studies with 213 LQTS patients showed that sodium channel blockers significantly shortened QTc by nearly 50 ms (MD -49.43, 95%CI -57.80 to -41.05, P<0.001), reduced the incidence of CEs (OR 0.12, 95%CI 0.04 to 0.32, P<0.001) and the proportion of QTc≥500 ms (OR 0.15, 95%CI 0.09 to 0.26, P<0.001), and increased the proportion of QTc≤460 ms (OR 18.00, 95%CI 7.49 to 43.26, P<0.001). Sodium channel blockers significantly shortened QTc both in LQT3 and non-LQT3 patients, while the QTc shortening effect in LQT3 was superior to that in non-LQT3 (57.39 ms vs. 36.61 ms). Mexiletine, flecainide, and ranolazine all significantly shortened QTc, and the QTc shortening effect by mexiletine was the best (60.70 ms vs. 49.08 ms vs. 50.10 ms). Conclusions: sodium channel blockers can be useful both in LQT3 and non-LQT3 patients. Mexiletine, flecainide and ranolazine significantly shortened QTc in LQTS patients, and the QTc shortening effect by mexiletine was the best.
Role of activation of the coagulation system in the pathogenesis of urticariaTaro Yasuma,1 Corina N. D’Alessandro-Gabazza,1 Tetsu Kobayashi,2 John Morser,3 Esteban C Gabazza.1*1Department of Immunology,2Department of Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, and Mie University Hospital, Edobashi 2-174, Tsu, Mie 514-8507, Japan.3Division of Hematology, Stanford University School of Medicine, 291 Campus Drive, Stanford, CA 94305, United States*Correspondence: Esteban C Gabazza, MD, PhD, Department of Immunology, Mie University Graduate School of Medicine, Edobashi 2-174, Postal Code 514-8507, Tsu-city, Mie, Japan. Tel.: +81 59 231 5017; fax: +81 59 231 5225.E-mail:email@example.comWord count: 590
Introduction Type 2 diabetes mellitus (T2DM) frequently associates with increasing multi-morbidity/treatment complexity. Some headway has been made to identify genetic and non-genetic risk factors for T2DM. However longitudinal clinical histories of individuals both before and after diagnosis of T2DM are likely to provide additional insight into both diabetes aetiology/further complex trajectory of multi-morbidity. Methods This study utilised diabetes patients/controls enrolled in the DARE (Diabetes Alliance for Research in England) study where pre- and post-T2DM diagnosis longitudinal data was available for trajectory analysis. Longitudinal data of 281 individuals (T2DM n=237 vs matched non-T2DM controls n=44) were extracted, checked for errors and logical inconsistencies and then subjected to Trajectory Analysis over a period of up to 70 years based on calculations of the proportions of most prominent clinical conditions for each year. Results For individuals who eventually had a diagnosis of T2DM made, a number of clinical phenotypes were seen to increase consistently in the years leading up to diagnosis of T2DM. Of these documented phenotypes, the most striking were diagnosed hypertension (more than in the control group) and asthma. This trajectory over time was much less dramatic in the matched control group. Immediately prior to T2DM diagnosis a greater indication of ischaemic heart disease proportions was observed. Post-T2DM diagnosis, the proportions of T2DM patients exhibiting hypertension and infection continued to climb rapidly before plateauing. Ischaemic heart disease continued to increase in this group as well as retinopathy, impaired renal function and heart failure. Conclusion These observations provide an intriguing and novel insight into the onset and natural progression of T2DM. They suggest an early phase of potentially-related disease activity well before any clinical diagnosis of diabetes is made. Further studies on a larger cohort of DARE patients are underway to explore the utility of establishing predictive risk scores.
Abstract Aim: To investigate the health care utilization and drug consumption of patients with fibromyalgia (FM). Materials and Methods: This is a cross-sectional study using the Clalit Health Care database. Clalit is the largest HMO in Israel, serving more than 4.4 million enrollees. We identified FM patients and age and sex-matched controls. Indicators of healthcare utilization and drug consumption were extracted and analyzed for both groups. Results: The study included 14,296 FM patients and 71,324 controls. The mean age was 56 years, with a female predominance of 92%. The mean number of visits across of all healthcare services (hospitalizations, emergency department visit, general practitioner clinic visits, rheumatology clinic visits and pain clinic visits) and the mean difference (MD) were significantly higher for FM patients compared to controls (MD 0.66, p<0.001; MD 0.23, p<0.001; MD 7.49, p<0.001; MD 0.31, p<0.001; MD 0.13, p<0.001), respectively. Drug use was significantly and consistently higher among FM patients compared to controls; NSAIDs (non-steroidal anti-inflammatory drugs) OR 2.56, P<0.001; Opioids OR 4.23, P<0.001; TCA (tricyclic antidepressants) OR 8.21, P<0.001; Gabapentinoids OR 6.31, P<0.001; SSRI (selective serotonin reuptake inhibitors) OR 2.07, P<0.001; SNRI (serotonin-norepinephrine reuptake inhibitor) OR 7.43, P<0.001. Conclusion: Healthcare utilization and drug use are substantially higher among patients with fibromyalgia compared to controls
Leptospirosis is a zoonotic neglected disease of worldwide public health concern. Leptospira species can infect a wide range of wild and domestic mammals and can lead to a spectrum of disease, including severe and fatal forms. Herein, we report for the first time a fatal Leptospira interrogans infection in a free-ranging nonhuman primate (NHP), a black-tufted marmoset. Icterus, pulmonary hemorrhage, interstitial nephritis and hepatocellular dissociation were the main findings raising the suspicion of leptospirosis. Diagnostic confirmation was based on specific immunohistochemical and PCR assays for Leptospira species. Immunolocalization of leptospiral antigens and identification of pathogenic species ( L. interrogans species) were important for better understanding the pathogenesis of disease. One Health related implications of free-ranging NHPs in anthropized areas and transmission dynamics of human and animal leptospirosis are discussed.
Title Page: MinicommentaryThis is a minicommentary on Reid et al. “How common are complications following polypropylene mesh, biological xenograft 3 and native tissue surgery for pelvic organ prolapse? A secondary analysis from the PROSPECT trial”.Title: Understanding Risk: a substitute for Information?Author : Swati Jha (MD, FRCOG)Consultant Gynaecologist and Honorary Senior Clinical Lecturer, Sheffield University. Subspecialist in UrogynaecologyInstitute : Department of Urogynaecology, Sheffield Teaching Hospitals NHS Foundation TrustAddress : Sheffield Teaching Hospitals, Level 4, Jessop Wing, Tree Root Walk, Sheffield. S10 2SFSwati.Jha1@nhs.net0044 (0)114 2268568Fax : 0114 2268165
Dobhoff tubes, used for post-pyloric feedings, have a weighted metal end with a small diameter that enhances their flexibility to traverse the gastrointestinal tract. Unfortunately, the metal stylet can iatrogenically perforate surrounding structures in patients with diminished cough and gag (1); and extreme caution should be considered before its utilization.
Aim To describe the antiepileptic drug (AED) prescription pattern in pregnant women and women of childbearing age in the 2010-2019 period in the Lombardy region, Italy. Methods The Lombardy region administrative healthcare databases (2010-2019) were analysed. AEDs were classified as drugs belonging to the N03A subgroup of the Anatomical Therapeutic Chemical Classification System. Women 15-49 years old were considered as women of childbearing age, while exposure during pregnancy was estimated taking into account the 12 months before delivery (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM codes in the diagnosis record from 650 to 659). Results During 2019, 16,605 women of childbearing age (prevalence: 14.8‰) received at least one AED prescription. Pregabalin was the most widely used antiepileptic in women of childbearing age (22.3%), followed by valproic acid (20.0%). The prevalence of AED prescription in pregnant women was 3.8‰, and levetiracetam and lamotrigine (16.6%) were the most commonly prescribed drugs. The prevalence of AED prescription did not change from 2010 to 2019 in women of childbearing age or in pregnant women. Valproic acid was one of the most used AEDs in pregnancy until 2016, after which its prescription declined from 19% to 14% of AED users. Conclusions Despite the decrease in valproic acid prescription over time, this drug is still among the most used AEDs, in particular in women of childbearing age. Educational interventions for healthcare professionals and women are needed in order to reduce the risk of unplanned pregnancy.
Background: Concern exists regarding adequacy of visualization of stress echocardiograms performed without intravenous contrast in persons with Class III obesity (body mass index ≥ 40 kg/m2). Methods: Dobutamine stress echocardiography (DSE) was performed on 128 candidates for bariatric surgery with class III obesity without chest pain or pre-existent coronary artery disease (CAD). DSE without intravenous contrast was initially performed on 62 patients with class III obesity, then was subsequently was performed with intravenous contrast on 66 patients with class III obesity. Left ventricular (LV) regional wall motion was assessed at baseline and peak stress using the 16-segment model. Results: In the intravenous contrast group 1046 of 1056 LV segments studied (99.1%) were well-visualized and interpretable at baseline and 1044 of 1056 LV segments studied (98.9%) were well-visualized and interpretable at peak stress. In the non-contrast group 905 of 992 segments studied (91.2%) were well-visualized and interpretable at baseline and 886 of 992 segments studied (89.3%) were well-visualized and interpretable at peak stress. A significantly greater number of LV segments were well-visualized and interpretable in the intravenous contrast group than in the group compared to the non-contrast group, at baseline and at peak stress (p < 0.00001 for both). DSE was positive for ischemia in 1 patient. All patients underwent bariatric surgery without cardiovascular complications. Six months after surgery, all patients were alive; none developed cardiovascular events. Conclusion: The use of intravenous contrast during DSE significantly improves visualization and interpretability of LV segments in patients with class III obesity.
Background Pericardiectomy for post-radiation constrictive pericarditis has been reported to generally have unfavorable outcomes. This study sought to evaluate surgical outcomes in a large cohort of patients undergoing pericardiectomy for radiation-associated pericardial constriction. Methods A retrospective analysis of all patients (≥18years) who underwent pericardiectomy for a diagnosis of constrictive pericarditis with a prior history of mediastinal irradiation from June 2002 to June 2019 was conducted. There were 100 patients (mean age 57.2±10.1 years, 49% females) who met the inclusion criteria. Records were reviewed to look at surgical approach, extent of resection, early mortality and late survival. Results The overall operative mortality was 10.1% (n=10). The rate of operative mortality decreased over the study period; however, the test of trend was not statistically significant (P=0.062). Hodgkin’s disease was the most common malignancy (64%) for which mediastinal radiation had been received. Only 27% patients had an isolated pericardiectomy, and concomitant pericardiectomy and valve surgery was performed in 46% patients. Radical resection was performed in 50% patients, whereas 47% patients underwent a subtotal resection. Prolonged ventilation (26%), atrial fibrillation (21%) and pleural effusion (16%) were the most common post-operative complications. The overall 1,5- and 10-years survival was 73.6%, 53.4% and 32.1% respectively. Increasing age (HR 1.044, 95%CI 1.017-1.073) appeared to have a significant negative effect on overall survival in the univariate model. Conclusion Pericardiectomy performed for radiation associated constrictive pericarditis has poor long-term outcomes. The early mortality, though high (~10%), has been showing a decreasing trend in the test of time.
Arteriovenous malformation of the pancreatic head is a relatively rare disease that can cause gastrointestinal bleeding and abdominal pain and requires appropriate and prompt treatment. Herein, we discuss the clinical presentation and management of a patient with arteriovenous malformation of the pancreatic head.
The state function based on fatigue accumulation model has a great influence on accuracy of fatigue reliability analysis of components. A nonlinear fatigue accumulation model considering the interaction of loads is proposed in this paper. By introducing the square ratio of front and back loads as the new load interaction factor into the conventional toughness exhaustion model, thus it is improved to reflect the load sequence and interaction effect simultaneously. Moreover, the fatigue state function based on proposed model is constructed, which is analyzed by the probability density evolution method. The time-varying fatigue reliability curve is obtained by analyzing the generalized density evolution equation. The proposed model are verified using four experimental data, and results shows that the predication residual life fraction such obtained is more accurate. And accuracy and efficiency of the proposed time-varying fatigue reliability analysis method is validated using multi-level loading experimental data.
Helminth diseases have long been a threat to the health of humans and animals. Roundworms are important organisms for studying parasitic mechanisms, disease transmission and prevention. The study of parasites in the giant panda is of importance for understanding how roundworms adapt to the host. Here, we report a high-quality chromosome-scale genome of Baylisascaris schroederi with a genome size of 253.60 Mb and 19,262 predicted protein-coding genes. We found that gene families related to epidermal chitin synthesis and environmental information processes in the roundworm genome have expanded significantly. Furthermore, we demonstrated unique genes involved in essential amino acid metabolism in the B. schroederi genome, inferred to be essential for the adaptation to the giant panda-specific diet. In addition, under different deworming pressures, we found that four resistance-related genes (glc-1, nrf-6, bre-4 and ced-7) were under strong positive selection in a captive population. Finally, 23 known drug targets and 47 potential drug target proteins (essential homologues linked to lethal phenotypes) were identified. The genome provides a unique reference for inferring the early evolution of roundworms and their adaptation to the host. Population genetic analysis and drug sensitivity prediction provide insights revealing the impact of deworming history on population genetic structure of importance for disease prevention.
Aim: To examine the incidence and treatment of acute myocardial infarction (AMI) as well as 30-day and 1-year prognoses of patients in three major regions of Hungary by analysing data from the country’s continuous and mandated infarction registry. Methods and results: The total population of Hungary is currently 9.8 million: 39% live in the eastern region (ER), 31% in the Central region (CR) and 30% in the western region (WR). These regions exhibited significant differences in income and people exposed to poverty. Population over 30 years, the age-standardised incidence of AMI was 177.5 (175.7–179.3) per 100,000 person-year. During hospital treatment, 82.5%–84.6% of patients with ST-elevation (STEMI) and 54.8%–81.8% without ST-elevation (NSTEMI) underwent PCI. The total ischaemic time was shortest in WR:221 minutes. In the STEMI group, the 30-day mortality rates of males were lowest in the WR (p = 0.03). If PCI was performed, mortality rates for both sexes were lowest in the WR (p < 0.01; p = 0.04). The 1-year mortality rate in the male population who received PCI was lowest in the WR. In the NSTEMI group, the 30-day mortality rate exhibited no differences. Regarding 1-year mortality, those who underwent PCI in the WR showed the lowest mortality. Conclusion: The major regions of Hungary exhibited significant differences regarding the prehospital delay, the incidence, treatment and mortality of AMI. Logistic regression analysis confirmed the independent prognostic significance of the region on the 30-day mortality of patients with STEMI (Hazard ratio = 0.88, p = 0.0114).
Experimenters face challenges and limitations while analyzing glycoproteins due to their high flexibility, stereochemistry, anisotropic effects, and hydration phenomena. Computational studies complement experiments and have been used in characterization of the structural properties of glycoproteins. However, recent investigations revealed that computational studies face significant challenges as well. Here, we introduce and discuss some of these challenges and weaknesses in the investigations of glycoproteins. We also present requirements of future developments in computational biochemistry and computational biology areas that could be necessary for providing more accurate structural property analyses of glycopro-teins using computational tools. Further theoretical strategies that need to be and can be developed are discussed herein.
Introduction: Although prolonged respiratory symptoms following SARS-CoV-2 infection have been reported in adults, there is a paucity of literature describing post-acute symptoms in pediatric patients following COVID-19. In this study we describe health data and respiratory findings in pediatric patients presenting with complaints of persistent respiratory symptoms following acute COVID-19 infection. Methods: This study included patients referred to Pulmonary Clinic at the Children’s Hospital of Philadelphia between December 2020 and April 2021 (n=29). Inclusion criteria included a history of SARS-CoV-2 RNA positivity or confirmed close household contact. A retrospective chart review was performed and demographic, clinical, imaging, and functional test data were collected. Results: The mean age at presentation to clinic was 13.1 years (range: 4-19 years). Patients had persistent respiratory symptoms ranging from 1.3 to 6.7 months post-acute infection. Persistent dyspnea and/or exertional dyspnea were present in nearly all (96.6%) of the patients at the time of clinic presentation. Other reported chronic symptoms included cough (51.7%) and exercise intolerance (48.3%). Fatigue was reported in 13.7% of subjects. Many subjects were overweight or obese (62.1%) and eleven subjects had a prior history of asthma. Lung function was normal in most patients. The six-minute walk test (6MWT) revealed exercise intolerance and significant tachycardia in two-thirds of children tested. Conclusion: Exertional dyspnea, cough and exercise intolerance were the most common respiratory symptoms in children with post-acute COVID-19 respiratory symptoms seen in an outpatient pulmonary clinic. Lung function, however, was mostly normal, and exertional intolerance was frequently demonstrated using the 6MWT.
Background: Many European health institutions have appointed multidisciplinary teams for the general management of vascular access to help improve efficiency, patient safety and reduce costs. Vascular access teams (VATs), or infusion teams, are specifically trained groups of healthcare professionals who assess, place, manage and monitor various outcomes and aspects of vascular access care. Objective: To assess the current landscape of vascular access management as a discipline across Europe. Methods: A Faculty of European VAT leads and experts developed a survey of 20 questions which was disseminated across several European countries. Questions focused on respondent and institution profile, vascular access device selection and placement, monitoring and reporting of complications, and access to training and education. The 1449 respondents included physicians, nurses, anaesthetists, radiologists and surgeons from public and private institutions ranging in size. Results: Availability of dedicated VATs vary by country, institution size, and institution type. Institutions with a VAT are more likely to utilise a tool (e.g., algorithm or guideline) to determine the appropriate vascular access device (55% vs 38%, p < 0.0002) and to have feedback on systematic monitoring of complications (40% vs 28%, p = 0.015). Respondents from institutions with a VAT are more likely to have received training on vascular access management (79% vs 53%, p < 0.0001) and indicated that the VAT was a source of support when difficulties arise. Conclusion: The survey results highlight some of the potential benefits of implementing a dedicated VAT including use of a broader range of vascular access devices, increased awareness of the presence of vascular access policies, increased likelihood of recent vascular access training, and increased rates of systematic monitoring of associated complications. The study reveals potential areas for further focus in the field of vascular access care, specifically examining the direct impact of vascular access teams.